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| 1.
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Hoshikawa, Takaya ; Tanji, Kei ; Matsuo, Jun-ichi ; Ishibashi, Hiroyuki
概要:
Intramolecular [2+2] cycloaddition of γ,δ-unsaturated ketenes derived from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with complete regioselectivity. © 2012 The Pharmaceutical Society of Japan.
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| 2.
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Nishida, Yuki ; Miyamori, Hisashi ; Thompson, Erik W. ; Takino, Takahisa ; Endo, Yoshio ; Sato, Hiroshi
概要:
金沢大学がん研究所がん病態制御<br />The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP
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(MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2. ©2008 American Association for Cancer Research.全文公開200911
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| 3.
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Nakamura, Akiko ; Nakajima, Miki ; Higashi, Eriko ; Yamanaka, Hiroyuki ; Yokoi, Tsuyoshi
概要:
医薬保健研究域薬学系<br />OBJECTIVES: Human uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) plays important roles in the
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metabolism of some clinical drugs, carcinogens, and steroid hormones. The molecular mechanisms of the inducible expression of UGT2B7 in response to xenobiotics have not been fully clarified. We sought to investigate whether the UGT2B7 is under the control of NF-E2 p45-related factor 2 (Nrf2), a key transcriptional factor regulating the expression of cytoprotective enzymes. METHODS: HepG2, HuH7, HLE, and Caco-2 cells were treated with sulforaphane (SFN), and the UGT2B7 mRNA levels were determined by real-time reverse transcriptase PCR. These cells were genotyped for the UGT2B7*2 (H268Y) allele using the PCR-restriction fragment length polymorphism method. Luciferase analyses and gel shift analyses were performed to identify the responsive regions for Nrf2 signaling. RESULTS: The UGT2B7 mRNA was induced by SFN in HepG2 and HuH7 genotyped as UGT2B7*1/*1, but not in HLE and Caco-2 cells genotyped as UGT2B7*2/*2. In HepG2 cells, the UGT2B7 protein level and morphine glucuronosyltransferase activity were also significantly induced by SFN. The induction was prominently decreased with small interfering RNA for Nrf2. In the 5'-flanking region (-2.5 kb) of the UGT2B7*2 allele, a 324-base pair insertion at -2067 and 12 single nucleotide polymorphisms simultaneously existed. Luciferase analyses and gel shift analyses revealed that an antioxidant responsive element at -1170 was responsible for the transactivation by Nrf2. In addition, a region from -990 to -858 on the UGT2B7*1 allele was also responsible for the transactivation by Nrf2. Abrogation of the Nrf2-dependent transactivation of the UGT2B7*2 allele was owing to the single nucleotide polymorphism -900A>G. CONCLUSION: UGT2B7 is transcriptionally regulated by Nrf2, but the mechanism is hindered by polymorphisms in the promoter region of UGT2B7*2. The allele-specific mechanism may cause variability of the glucuronidation in response to oxidative stress.全文公開200908
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| 4.
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Yamada, Fumio ; Kawanishi, Atsuko ; Tomita, Akiko ; Somei, Masanori
概要:
1-Hydroxy-2,3-dimethylindole (1) has been prepared for the first time. Under atmospheric oxygen, 1 was converted rapidly into 3-hydroxy-2,3-dimethyl- 3H-indole N-oxide (2). The structure was deduced, based on its products obtained
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by the reaction with Ac2O in pyridine and confirmed by X-ray single crystallographic analysis.
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| 5.
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Nakano, Takeo ; Soeta, Takahiro ; Endo, Kohei ; Inomata, Katsuhiko ; Ukaji, Yutaka
概要:
The sequential 1,4-elimination reaction of (E)-4-alkoxy-2-butenyl benzoates and [1,2]-Wittig rearrangement gave (2Z,4E)-
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2,4-pentadien-1-ols stereoselectively. Z-Selective formation of intermediary vinyl ethers, whose stereochemistry was well elucidated by the "syn-effect", was achieved by treatment of the 2-butenyl benzoates with KOH in the presence of Pd catalyst. The subsequent [1,2]-Wittg rearrangement by use of n-BuLi proceeded with retention of the stereochemistry of the intermediary vinyl ethers. © 2013 American Chemical Society.
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| 6.
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Higuchi, Akihiro ; Erina Oonishi ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: 2-hydroxy estradiol (2-OHE2) is a catechol derivative of 17β -Estradiol (E2) and it is s
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ynthesized from E2 catalyzed by cytochrome P4501A1. Previous studies reported that 2-OHE2 is a physiologic antioxidant in lipoproteins, liver microsomes, and the brain. Catechol derivatives show an anti-inflammatory effect through the inhibition of prostaglandin endoperoxide synthase (PGS) activity. Corneal erosion caused by dry eye is related to an increase in oxidative stress and inflammation in ocular surface cells. We investigated the therapeutic effects of 2-OHE2 on corneal damage caused by dry eye. Methods: Steroidal radical scavenging activity was confirmed through the electron spin resonance (ESR) method. PGS activity was measured using the COX Fluorescent Activity Assay Kit. To evaluate the effect of 2-OHE2 on the treatment for dry eye, 2-OHE2 was applied as an eye drop experiment using dry eye model rats. Results: 2-OHE2 scavenged tyrosyl radical and possibly suppressed oxidative stress in corneal epithelial cells. In addition, 2-OHE2 inhibited PGS activity, and 2-OHE2 is probably a competitive inhibitor of PGS. Corneal PGS activity was upregulated in the dry eye group. Therefore, 2-OHE2 eye drops improved corneal erosion in dry eye model rats. Conclusions: 2-OHE2 is a candidate for the treatment of dry eye through the suppression of inflammation and oxidative stress in the cornea. © 2016 Molecular Vision.
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| 7.
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Nakata, Shunji ; Kato, Takashi ; Ozaki, Shinya ; Kawae, Takeshi ; Morimoto, Akiharu
概要:
Thin film Al2O3/Al-rich Al2O 3/SiO2 structures were fabricated on p-Si substrates. Radio-frequency magnetron co-sputteri
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ng was used to form Al-rich Al 2O3 thin film as the charge-trapping layer of nonvolatile Al2O3 memory. Capacitance-voltage measurements showed a large hysteresis due to charge trapping in the Al-rich Al2O 3 layer. The charge trap density was estimated to be 42.7 × 1018 cm- 3, which is the largest value ever reported for an Al-rich Al2O3 layer; it is six times larger than that of a conventional metal-nitride-oxide-silicon memory. Thermal annealing was found to reduce the leakage current of the Al2O3 blocking layer, thereby providing this structure with better data retention at room temperature than an as-deposited one. In addition, the annealed structure was found to exhibit good data retention even at 100 C. © 2013 Elsevier B.V. All rights reserved.
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| 8.
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Inami, Shinnosuke ; Nishio, Masaki ; Hayashi, Yoshihito ; Isobe, Kiyoshi ; Kameda, Hiroyuki ; Shimoda, Tatsuya
概要:
金沢大学理工研究域物質化学系<br />An all-inorganic complex, [Mn2{(CVO3) 5}2]6- (1), was synthesized, and the structure determination r
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eveals a dinuclear manganese complex coordinated by two cyclic pentavanadate ligands. The cyclic pentavanadate units sandwich the edge-sharing octahedral dimanganese core through, coordination of the oxido group of the pentavanadate. A. dinuclear cobalt complex with, a cyclic decavanadate, [Co 2(OH2)2(VO3)10]6- (2), was also synthesized. The structure analysis reveals a dinuclear cobalt complex with a macrocyclic decavanadate, which is composed of 10 VO4 units joined by the vertex. Sharings. The CoO6 octahedrons are edge-shared, with each cobalt octahedron coordinated to five oxido groups from the decavanadate. The remaining site is occupied by - water. The coordinated water molecules are supported with hydrogen bonds in two directions. Complex 2 in acetonitrile shows no reactivity with dioxygen even at low temperature, and the cyclic voltammogram of 2 shows no redox chemistry in acetonitrile. Complex 2 exhibits chromism by water exposure both, in the solid state and. in acetonitrile. Complex 2 is green-yellow in color, and. the addition of water causes the complex to turn brown. After heating the sample, it returns to its original color in a reversible manner. The EXAFS data in acetonitrile is also reported, and is consistent with the solid-state structure. © Wiley-VCH Verlag GmbH & Co. KGaA.
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| 9.
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Sawanomukai, Takashi ; Iwatsubo, Yoshikane ; Naruhashi, Naohiro
概要:
Chromosome counts of 16 species and two varieties of Scutellaria（Lamiaceae）collected from 45 localities in Ja-pan were r
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eported. First counts were the following 11 taxa : S . amabilis（2n=26）, S . brachyspica（2n=26）, S . in-dica var. parvifolia（2n=26）, S . iyoensis（2n=26）, S . kiusiana（2n=26）, S . laeteviolacea var. laeteviolacea（2n =26）, S . laeteviolacea var. maekawae（2n=26）, S . muramatsui（2n=26）, S . pekinensis var. transitra（2n=28）, S . shikokiana（2n=28）and S . tsusimensis（2n=26）. New counts were reported in S . dependens（2n=28）, S . strigil-losa（2n=30）and S . yezoensis（2n=30）. Chromosome counts for S . barbata（2n=26）, S . guilielmii（2n=28）, S . indica var. indica（2n=26）and S . rubropunctata var. rubropunctata（2n=26）were confirmed.
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| 10.
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Matsuo, Jun-ichi ; Okuno, Ryosuke ; Takeuchi, Kosuke ; Kawano, Mizuki ; Ishibashi, Hiroyuki
概要:
金沢大学医薬保健研究域薬学系<br />Optimized reaction conditions for the preparation of various 2-monosubstituted 3-ethoxycyclobutanone
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s are described. 2-Monoalkyl 3-ethoxycyclobutanones were efficiently prepared by the reaction of the corresponding carboxylic acid chlorides and an excess amount of ethyl vinyl ether in the presence of diisopropylethylamine at 90 °C in a sealed tube. 2-Monoaryl 3-ethoxycyclobutanones were prepared by using 2,6-lutidine as a base in the above-mentioned procedure. © 2010 Published by Elsevier Ltd. All rights reserved.
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| 11.
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Matsuo, Junichi ; Okuno, Ryosuke ; Takeuchi, Kosuke ; Kawano, Mizuki ; Ishibashi, Hiroyuki
概要:
金沢大学医薬保健研究域薬学系<br />Optimized reaction conditions for the preparation of various 2-monosubstituted 3-ethoxycyclobutanone
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s are described. 2-Monoalkyl 3-ethoxycyclobutanones were efficiently prepared by the reaction of the corresponding carboxylic acid chlorides and an excess amount of ethyl vinyl ether in the presence of diisopropylethylamine at 90 °C in a sealed tube. 2-Monoaryl 3-ethoxycyclobutanones were prepared by using 2,6-lutidine as a base in the above-mentioned procedure. © 2010 Elsevier Ltd. All rights reserved.
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| 12.
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Nishida, Y. ; Miyamori, H. ; Thompson, E.W. ; Takino, Takahisa ; Sato, H.
概要:
Division of Molecular Viology and Oncology
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| 13.
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Yokota, Shinichi ; Higashi, Eriko ; Fukami, Tatsuki ; Yokoi, Tsuyoshi ; Nakajima, Miki
概要:
金沢大学医薬保健研究域薬学系<br />Human CYP2A6 is responsible for the metabolism of nicotine and coumarin as well as the metabolic act
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ivation of tobacco-related nitrosamines. Earlier studies revealed that CYP2A6 activity was increased by dietary cadmium or cruciferous vegetables, but the underlying mechanisms remain to be clarified. In the present study, we investigated the possibility that Nrf2 might be involved in the regulation of CYP2A6. Real-time RT-PCR analysis revealed that the CYP2A6 mRNA level in human hepatocytes was significantly (P < 0.01, 1.4-fold) induced by 10 μM sulforaphane (SFN), a typical activator of Nrf2. A computer-based search identified three putative antioxidant response elements (AREs) in the 5′-flanking region of the CYP2A6 gene at positions -1212, -2444, and -3441, termed ARE1, ARE2, and ARE3, respectively. Electrophoretic mobility shift assays demonstrated that Nrf2 bound only to ARE1. Luciferase assays using HepG2 cells revealed that the overexpression of Nrf2 significantly increased the reporter activities of the constructs containing a 30-bp fragment that included ARE1. However, the activity of the construct containing the intact 5′-flanking region (-1 to -1395) including ARE1 was not increased by the overexpression of Nrf2. In contrast, when the reporter construct was injected into mice via the tail vein, the reporter activity in the liver was significantly (P < 0.05, 1.9-fold) increased by SFN (1 mg/head) administration. In conclusion, we found that human CYP2A6 is regulated via Nrf2, suggesting that CYP2A6 is induced under oxidative stress. © 2010 Elsevier Inc. All rights reserved.
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| 14.
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Watanabe, Hiroyuki ; Okada, G. ; Ohtsubo, K. ; Yao, F. ; Jiang, P.H. ; Sawabu, Norio
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| 15.
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Okado, Ryohei ; Nowaki, Aya ; Matsuo, Jun-ichi ; Ishibashi, Hiroyuki
概要:
A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates,
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whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters.
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| 16.
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Miyamoto, Yoshiaki ; Wada, Norihiro ; Soeta, Takahiro ; Fujinami, Shuhei ; Inomata, Katsuhiko ; Ukaji, Yutaka
概要:
The stereoselective direct transformation of N-(propargylic)hydroxylamines into cis-2-acylaziridines was achieved by the
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combined use of AgBF4 and CuCl. Copper salts were found to promote the transformation of the intermediary 4-isoxazolines into 2-acylaziridines and both 3-aryl- and 3-alkyl-substituted 2-acylaziridines could be prepared by using this method. Furthermore, subsequent 1,3-dipolar cycloaddition of azomethine ylides that were generated in situ from the intermediary 2-acylaziridines with maleimides was achieved in a stereoselective one-pot procedure to afford the corresponding 2-acylpyrrolidines, which consisted of an octahydropyrrolo[3,4-c]pyrrole skeleton. Love the way ylide: The transformation of N-(propargylic) hydroxylamines into cis-2-acylaziridines and subsequent 1,3-dipolar cycloaddition of the in situ generated azomethine ylides with maleimides stereoselectively afforded 2-acylpyrrolidines. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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| 17.
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Popivanova, Boryana K. ; Kostadinova, Feodora I. ; Mukaida, Naofumi
概要:
Azoxymethane (AOM) administration followed by repetitive dextran sulfate sodium (DSS) ingestion causes chronic colonic inflammation with macrophage infiltration and enhanced expression of a macrophage-tropic chemokine, CCL2, in wild-type
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(WT) mice. These mice eventually develop multiple colon tumors. In contrast, mice deficient in CCR2, a specific receptor for CCL2, exhibited less macrophage infiltration and attenuated tumor formation. WT mice transplanted with CCR2-deficient bone marrow developed fewer tumors after AOM and DSS treatment than either WT or CCR2-deficient mice transplanted with WT bone marrow. Furthermore, when injected to WT mice with multiple colon tumors, a CCL2 antagonist expression vector attenuated macrophage and granulocyte infiltration, and eventually reduced the numbers and sizes of tumors. These results implied the crucial involvement of the CCL2-CCR2 interactions in the development and progression of colon carcinoma associated with chronic inflammation.
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| 18.
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Begum, Zinnat A. ; Rahman, Ismail M. M. ; Tate, Yousuke ; Egawa, Yuji ; Maki, Teruya ; Hasegawa, Hiroshi
概要:
The protonation and complex formation equilibria of two biodegradable aminopolycarboxylate chelants {dl-2-(2-carboxymeth
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yl)nitrilotriacetic acid (GLDA) and 3-hydroxy-2,2′-iminodisuccinic acid (HIDS)} with Ni 2+, Cu 2+, Zn 2+, Cd 2+ and Pb 2+ ions were investigated using the potentiometric method at a constant ionic strength of I = 0.10 mol·dm -3 (KCl) in aqueous solutions at 25 ± 0.1 °C. The stability constants of the proton-chelant and metal-chelant species for each metal ion were determined, and the concentration distributions of various complex species in solution were evaluated for each ion. The stability constants (log 10K ML) of the complexes containing Ni 2+, Cu 2+, Zn 2+, Cd 2+ and Pb 2+ ions followed the identical order of log 10K CuL > log 10K NiL > log 10K PbL > log 10K ZnL > log 10K CdL for either GLDA (13.03 > 12.74 > 11.60 > 11.52 > 10.31) or HIDS (12.63 > 11.30 > 10.21 > 9.76 > 7.58). In each case, the constants obtained for metal-GLDA complexes were larger than the corresponding constants for metal-HIDS complexes. The conditional stability constants (log 10 {Mathematical expression}) of the metal-chelant complexes containing GLDA and HIDS were calculated in terms of pH, and compared with the stability constants for EDTA and other biodegradable chelants. © 2012 Springer Science+Business Media New York.
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| 19.
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Begum, Zinnat A. ; Rahman, Ismail M. M. ; Tate, Yousuke ; Egawa, Yuji ; Maki, Teruya ; Hasegawa, Hiroshi
概要:
The protonation and complex formation equilibria of two biodegradable aminopolycarboxylate chelants {dl-2-(2-carboxymeth
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yl)nitrilotriacetic acid (GLDA) and 3-hydroxy-2,2′-iminodisuccinic acid (HIDS)} with Ni 2+, Cu2+, Zn2+, Cd2+ and Pb 2+ ions were investigated using the potentiometric method at a constant ionic strength of I = 0.10 mol·dm-3 (KCl) in aqueous solutions at 25 ± 0.1 C. The stability constants of the proton-chelant and metal-chelant species for each metal ion were determined, and the concentration distributions of various complex species in solution were evaluated for each ion. The stability constants (log10 K ML) of the complexes containing Ni2+, Cu2+, Zn2+, Cd2+ and Pb2+ ions followed the identical order of log10 K CuL > log10 K NiL > log10 K PbL > log10 K ZnL > log10 K CdL for either GLDA (13.03 > 12.74 > 11.60 > 11.52 > 10.31) or HIDS (12.63 > 11.30 > 10.21 > 9.76 > 7.58). In each case, the constants obtained for metal-GLDA complexes were larger than the corresponding constants for metal-HIDS complexes. The conditional stability constants (log10 $$ K-{\text{ML}}^{'} $$) of the metal-chelant complexes containing GLDA and HIDS were calculated in terms of pH, and compared with the stability constants for EDTA and other biodegradable chelants. © 2012 Springer Science+Business Media New York.
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| 20.
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図書
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Tadeusz Skorupski
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| 21.
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Kato, Takehiro ; Kotaka, Hiroki ; Ishii, Fumiyuki
概要:
Using first-principles method, we investigated the electronic states of Bi2Te3 and Bi2Se3. We showed that both Bi2Te3 an
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d Bi2Se3 are insulators with a bulk band gap. In contrast, the surface states of Bi2Te3 and Bi2Se3 films have a metallic band connecting the conduction and valence bands. The films have an energy gap at the (Formula presented.) point when the film thickness is less than four quintuple layers (QLs), or about 30 Å. The energy gaps are closed at six QLs and four QLs for Bi2Te3 and Bi2Se3, respectively. We confirmed the metallicity up to nine QLs. Furthermore, we investigated the spin structures of nine-QL films at the Fermi energy in momentum space. We found that both the Bi2Te3 and Bi2Se3 films have Rashba-type spin textures; i.e. the surface states have spin–polarisation. To investigate the spatial distribution of the spin, we decomposed the expected values of the spin for each atom. The expected values of the spin are localised within the third QL from the surface. Our results of nine-QL films clearly show the boundary between the bulk and surface regions.
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| 22.
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Echizen, Kanae ; Hirose, Osamu ; Maeda, Yusuke ; Oshima, Masanobu
概要:
Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2) play a key role in generation of the inflamm
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atory microenvironment in tumor tissues. Gastric cancer is closely associated with Helicobacter pylori infection, which stimulates innate immune responses through Toll-like receptors (TLRs), inducing COX-2/PGE2 pathway through nuclear factor-κB activation. A pathway analysis of human gastric cancer shows that both the COX-2 pathway and Wnt/β-catenin signaling are significantly activated in tubular-type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin-11, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor-promoting roles through a variety of mechanisms, is induced in a COX-2/PGE2 pathway-dependent manner in both human and mouse gastric tumors. Moreover, the COX-2/PGE2 pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX-2/PGE2-dependent mechanism. In contrast, disruption of Myd88 results in suppression of the inflammatory microenvironment in gastric tumors even when the COX-2/PGE2 pathway is activated, indicating that the interplay of the COX-2/PGE2 and TLR/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX-2/PGE2 pathway together with TLR/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer. © 2016 Japanese Cancer Association.
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| 23.
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Yamakawa, Daishi ; Kidoya, Hiroyasu ; Sakimoto, Susumu ; Jia, Weizhen ; Naito, Hisamichi ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells (ECs). It has dual roles
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in promoting angiogenesis and stabilizing blood vessels, and it has been suggested that Tie2 forms dimers and/or oligomers in the absence of angiopoietin-1 (Ang1); however, the mechanism of ligand-independent dimerization of Tie2 and its biological significance have not been clarified. Using a bimolecular fluorescence complementation assay and a kinase-inactive Tie2 mutant, we show here that ligand-independent Tie2 dimerization is induced without Tie2 phosphorylation. Moreover, based on the fact that Tie1 never forms heterodimers with Tie2 in the absence of Ang1 despite having high amino acid sequence homology with Tie2, we searched for ligand-independent dimerization domains of Tie2 by reference to the difference with Tie1. We found that the YIA sequence of the intracellular domain of Tie2 corresponding to the LAS sequence in Tie1 is essential for this dimerization. When the YIA sequence was replaced by LAS in Tie2 (Tie2YIA/LAS), ligand-independent dimer was not formed in the absence of Ang1. When activation of Tie2YIA/LAS was induced by a high dose of Ang1, phosphorylation of Tie2 was limited compared with wild-type Tie2, resulting in retardation of activation of Erk downstream of Tie2. Therefore, these data suggest that ligand-independent dimerization of Tie2 is essential for a strong response upon stimulation with high dose Ang1. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
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| 24.
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24. The Effect of Tree Planting within Roadside Green Space on Dispersion of CO2 from Transportation
Aini, Nurul ; Shen, Zhenjiang
概要:
Transportation has become one of the most significant contributors to CO2 in the world because of its fuel usage. Trees are planted on the roadside to reduce levels of CO2 in the air because trees have the ability to absorb CO2 to be used
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in the photosynthesis process. This ability will be maximized if the dispersion of CO2 is concentrated around the tree. However, there are some differing results from previous studies regarding this. Some research results have found trees can increase CO2 concentration and vice versa. Accordingly, this study aims to evaluate the effect of tree planting on the roadside in dispersing CO2 using a real 3D environment. The methods used in this research are CO2 emission analysis to obtain the amount of CO2. Then, Computational Fluid Dynamics (CFD) analysis is used to simulate the dispersion of CO2 in the study area both without trees and with trees. However, due to the mixing of air and CO2, this simulation uses a scalar mixing analysis. Some conditions are considered, such as the characteristics of buildings, the characteristics of trees, and environmental conditions. The result indicates that trees can decrease the velocity and increase the concentration of CO2 on the roadside but decrease CO2 concentration on the road. Tree planting can decrease the velocity by 4.3% in the value range 0.9-1 m/s. This condition increases CO2 concentration on the roadside. Trees can increase CO2 by 25% on the right of a roadside and increase CO2 concentration by 10% on the left side.
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| 25.
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Iwasaki, Yusaku ; Nakabayashi, Hajime ; Kakei, Masafumi ; Shimizu, Hiroyuki ; Mori, Masatomo ; Yada, Toshihiko
概要:
金沢大学医薬保健研究域医学系<br />Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and sev
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eral peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca2+ concentration ([Ca2+]i) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10-10-10-8 M increased [Ca2+]i in the isolated neurons in a concentration-dependent manner, and at 10-8 M it increased [Ca2+]i in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca2+-free conditions and by N-type Ca2+ channel blocker, ω-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited [Ca2+]i responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca2+ influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain. © 2009 Elsevier Inc. All rights reserved.
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| 26.
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論文
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Hinoi, Eiichi ; Wang, Liyang ; Fujimori, Sayumi ; Yoneda, Yukio
概要:
金沢大学医薬保健研究域薬学系<br />Nuclear factor E2-related factor 2 (nrf2) is accepted as an important transcription factor in the re
…
gulation of many phase II detoxifying enzymes and oxidative-stress-inducible genes in many tissues including bone and cartilage. However, little attention has been paid to precise role of nrf2 on osteoblasts and chondrocytes. In the present study, we therefore investigated the role of nrf2 in the regulation of cell proliferation, differentiation and maturation using both MC3T3-E1 and ATDC5 cells. In MC3T3-E1 cells stably transfected with nrf2 (MC3T3-E1-nrf2 clone), the differentiation-dependent induction of alkaline phosphatase activity was significantly inhibited in addition to decrease of the mineralized matrix formation. Moreover, expression of mRNAs for osteocalcin and type I collagen was also markedly attenuated in MC3T3E1-nrf2 clone but not in MC3T3E1-empty vector clone. These inhibitory effect on cell differentiation was also observed in ATDC5 cells stably transfected with nrf2. Moreover, nrf2 significantly impaired the runx2-dependent enhancement of osteocalcin promoter activity. These data suggest that nrf2 may negatively regulate the differentiation of both osteoblasts and chondrocytes through inhibition of the runx2 dependent transcriptional activity.
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| 27.
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論文
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27. Convenient synthetic method for 3-(3-substituted indol-2-yl)quinoxalin-2- ones as VEGF inhibitor
Aoki, Katsuyuki ; Koseki, Jun-ichi ; Takeda, Shuichi ; Aburada, Masaki ; Miyamoto, Kenichi
概要:
金沢大学医学部附属病院薬剤部<br />It has already been reported that 3-(indol-2-yl)quinoxalin-2-ones 1)? have a potent inhibitory effec
…
t on the growth of tumor cells based on anti-angiogenesis activity. We have also carried out a structure-activity relationship (SAR) study of 3-(indol-2-yl)quinoxalin-2-ones, which showed a potent inhibitory activity toward the vascular endothelial growth factor (VEGF)-induced proliferation of human mesangial cells and the VEGF-induced auto-phosphorylation of human umbilical vein endothelial cells.2) Moreover, one of these compounds has a potent medicinal effect based on anti-angiogenic action, by oral administration2) (Chart 1, 9). However, since the existing synthetic methods1) for the preparation of 3-(indol-2-yl)quinoxalin-2-ones consist of multiple steps some of which require strict anhydrous conditions, a convenient and simple synthetic method in place of the existing method is desirable. As a result of the investigations into the synthetic procedures, 3-(3-substituted indol-2-yl)quinoxalin-2-ones can be easily prepared by the condensation of 3-substituted indoles with quinoxalin-2-ones in the presence of trifluoroacetic acid (TFA). Herein, we report the examination of these reaction conditions and the application of this new synthetic method to the synthesis of the derivatives as VEGF inhibitors. © 2007 Pharmaceutical Society of Japan.
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| 28.
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論文
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Maeda, Hajime ; Matsuda, Shoji ; Mizuno, Kazuhiko
概要:
金沢大学理工研究域物質化学系<br />Photoreactions of 2-cyano-6-methoxynaphthalene with methoxy-substituted 1,2-diarylcyclopropanes in b
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enzene give 2-cyano-1-(1,3-diarylpropyl)-6-methoxynaphthalenes. The excellent regioselectivity seen in these processes can be explained by initial formation of singlet exciplexes, in which the dipoles of each component are oriented in opposite directions. © 2009 Elsevier B.V. All rights reserved.
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| 29.
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論文
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Matsuo, Jun-ichi ; Okuno, Ryosuke ; Ishibashi, Hiroyuki
概要:
2-Carbomethoxycyclobutanone reacted with N-phenyl-C-arylnitrones to afford methyl 5-oxo-2-[aryl(phenylamino)methyl]tetra
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hydrofuran-2-carboxylates by the catalysis of indium(III) triflate in the presence of magnesium sulfate. © 2012 Elsevier Ltd. All rights reserved.
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| 30.
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論文
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Matsuo, Jun-ichi ; Okuno, Ryosuke ; Ishibashi, Hiroyuki
概要:
2-Carbomethoxycyclobutanone reacted with N-phenyl-C-arylnitrones to afford methyl 5-oxo-2-[aryl(phenylamino)methyl]tetra
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hydrofuran-2-carboxylates by the catalysis of indium(III) triflate in the presence of magnesium sulfate. © 2012 Elsevier Ltd. All rights reserved.
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| 31.
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論文
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Yamada, Koji ; Somei, Masanori
概要:
Photoirradiation of 1-ethoxy-2-phenylindole in methanol and the reaction of 1-hydroxy-2-phenylindole with tosyl chloride
…
produced 6-ethoxy- and 6-tosyloxy-2-phenylindoles, respectively, as minor products. The latter was derived to 6-ethoxy-2-phenylindole. The structure is determined by direct comparison of the spectral data with those of the authentic 4-, 5-, 6-, and 7-ethoxy-2-phenylindoles whose syntheses are reported in detail. © 2012 The Japan Institute of Heterocyclic Chemistry.
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| 32.
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論文
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Ito, Tatsuro ; Sato, Jugo
概要:
TD-pairs of type II over C with shape 1, 2, ..., 2, 1 are classified by constructing all of them explicitly as certain s
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ort of tensor product of two L-pairs in a matrix form involving 8 parameters in addition to the diameter. Six of the 8 parameters describe the eigenvalues and the other two give the zeros of the Drinfel'd polynomial. © 2014 Elsevier Inc.
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| 33.
図書 |
図書
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European Monitoring Centre for Drugs and Drug Addiction
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| 34.
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論文
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Nakata, Shunji ; Maeda, Ryoji ; Kawae, Takeshi ; Morimoto, Akiharu ; Shimizu, Tatsuo
概要:
A thin-film structure comprising Al2O3/Al-rich Al2O3/SiO2 was fabricated on Si substrate. We used radio-frequency magnet
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ron co-sputtering with Al metal plates set on an Al2O3 target to fabricate the Al-rich Al2O 3 thin film, which is used as a charge storage layer for nonvolatile Al2O3 memory. We investigated the charge trapping characteristics of the film. When the applied voltage between the gate and the substrate is increased, the hysteresis window of capacitance-voltage (C-V) characteristics becomes larger, which is caused by the charge trapping in the film. For a fabricated Al-O capacitor structure, we clarified experimentally that the maximum capacitance in the C-V hysteresis agrees well with the series capacitance of insulators and that the minimum capacitance agrees well with the series capacitance of the semiconductor depletion layer and stacked insulator. When the Al content in the Al-rich Al2O3 is increased, a large charge trap density is obtained. When the Al content in the Al-O is changed from 40 to 58%, the charge trap density increases from 0 to 18 × 1018 cm-3, which is 2.6 times larger than that of the trap memory using SiN as the charge storage layer. The device structure would be promising for low-cost nonvolatile memory. © 2011 Elsevier B.V. All rights reserved.
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| 35.
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論文
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Nakano, Tomoyuki ; Shinsei, Naoki ; Ishida, Masahiro ; Tanaka, Yasunori ; Uesugi, Yoshihiko ; Ishijima, Tatsuo
概要:
This paper reports enhancement effect of N2/O2 gas addition in thermal plasma irradiation on the spallation phenomena fr
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om polyamide-66 (PA66) specimens with water absorption. The polyamide materials are widely used, for example, in low-voltage circuit breakers and arcing horns as ablation material. In such devices, the polymer is often contacted with arc discharges to be ablated, which increases the arc current interruption ability of the circuit breakers. In our previous experiments, not only ablation but also spallation phenomena had been found to occur from PA66 specimens with water absorption by Ar thermal plasma irradiation. The present work was conducted to investigate effect of N2/O2 inclusion in the irradiating thermal plasma on the occurrence of spallation phenomena because the air circuit breaker was used in air. Relative oxygen admixture ratio to N2 was changed from 0% to 100% with a fixed heat flux irradiated to PA66 specimens. Results indicated that O2 inclusion effectively promotes the frequency of spallation particle ejection from PA66 specimen with 3 wt% water absorption. © 2013 IEEE.
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| 36.
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論文
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Tang, Ning ; Sato, Kousuke ; Tokuda, Takahiro ; Tatematsu, Michiya ; Hama, Hirotaka ; Suematsu, Chikako ; Kameda, Takayuki ; Toriba, Akira ; Hayakawa, Kazuichi
概要:
Airborne particulates were collected at a background site (Wajima Air Monitoring Station; WAMS) on the Noto Peninsula, J
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apan from January 2006 to December 2007. 1-, 2-nitropyrenes (1-, 2-NPs) and 2-nitrofluoranthene (2-NFR), in the particulates were determined with a sensitive HPLC method with chemiluminescence detection. The average concentrations were higher in winter than in summer. A meteorological analysis indicated that the air samples collected in winter were transported mainly from Northeast China over the Japan Sea. Both the concentration ratios of 2-NFR to 1-NP and 1-NP to pyrene were similar to those in Shenyang in Northeast China which located along the air transportation route to WAMS, but not in Kanazawa which near WAMS. These results strongly suggest that most of the atmospheric 1-, 2-NPs and 2-NFR at WAMS in winter were long range transported from Northeast China. © 2014 Elsevier Ltd. All rights reserved.
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| 37.
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論文
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Yamada, Fumio ; Fukui, Yoshikazu ; Iwaki, Takako ; Ogasawara, Sachiko ; Okigawa, Masaki ; Tanaka, Satomi ; Somei, Masanori
概要:
A simple and new method for the preparation of optically active methyl 3a-chloro-, 3a-bromo-, 3a-hydroxy-, and 3a-alkoxy
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-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylates has been developed. © 2006 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 38.
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論文
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Yamaguchi, Junpei ; Sasaki, Motoko ; Sato, Yasunori ; Itatsu, Keita ; Harada, Kenichi ; Zen, Yoh ; Ikeda, Hiroko ; Nimura, Yuji ; Nagino, Masato ; Nakanuma, Yasuni
概要:
医薬保健研究域医学系<br />Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subunit of p
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olycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor suppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16INK4a, E-cadherin, and p21were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. © 2009 Japanese Cancer Association.
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| 39.
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Tao Le .
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| 40.
図書 |
図書
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edited by Jaap Mansfeld, David T. Runia
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| 41.
図書 |
図書
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寺田幸代[著]
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| 42.
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論文
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Pan, Haixiao ; Zheng, Yuming ; Wang, Zizhan
概要:
To explore the impact of geographical location, built environment, public transportation service and individual socioeco
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nomic attributes on commuting carbon dioxide (CO2) emissions, a survey was conducted in 27 residential compounds of Shanghai in 2016. In this paper, commuting distance was calculated according to a Baidu map application programming interface (API). CO2 emissions were calculated based on the mode used in each segment of commuting and distance travelled. Through the use of a multiple linear regression model, factors of personal socioeconomic attributes, including gender, occupation and apartment area, were significant to commuting CO2 emissions. In terms of the public transport service, the distance from compounds to the nearest metro station was found to be a significant factor on CO2 emissions, whereas the built environment, such as parking space and employment density, had a weak impact in our study. In addition, even when living near a metro station, the top 20% of travellers’ CO2 emissions can account for approximately 80% of the total CO2 emissions. Hence, policies to reduce those people’s commuting CO2 emissions are worth further exploring.
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| 43.
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論文
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Inoue, Daiki ; Kaido, Daisuke ; Yoshikawa, Yuta ; Minegishi, Mitsuyuki ; Matsumoto, Koichi ; Abe, Satoshi ; Murayama, Shigeyuki ; 松本, 宏一 ; 阿部, 聡
概要:
金沢大学理工研究域数物科学系<br />We have measured linear thermal expansion and magnetostriction of single crystal CeRu2Si2 that is we
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ll known as a heavy fermion metamagnetic compound. Thermal expansion and magnetostriction along the a-axis (B | a) and the c-axis (B | c) were measured by the capacitive dilatometer at temperatures down to 12 mK and in magnetic fields up to 9 T. We observed a strong anisotropy between a and c axis. In addition, negative deviations from Landau-Fermi liquid behavior for thermal expansion and magnetostriction coefficients were found below 50 mK and 0.4 T indicating non Fermi liquid behavior. © 2015 The Authors. Published by Elsevier B.V.<br />出版社版
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| 44.
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論文
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Lan, Fei ; Misu, Hirofumi ; Chikamoto, Keita ; Takayama, Hiroaki ; Kikuchi, Akihiro ; Mohri, Kensuke ; Takata, Noboru ; Hayashi, Hiroto ; Matsuzawa-Nagata, Naoto ; Takeshita, Yumie ; Noda, Hiroyo ; Matsumoto, Yukako ; Ota, Tsuguhito ; Nagano, Toru ; Nakagen, Masatoshi ; Miyamoto, Ken-ichi ; Takatsuki, Kanako ; Seo, Toru ; Iwayama, Kaito ; Tokuyama, Kunpei ; Matsugo, Seiichi ; Tang, Hong ; Saito, Yoshiro ; Yamagoe, Satoshi ; Kaneko, Shuichi ; Takamura, Toshinari
概要:
Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but
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the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance. © 2014 by the American Diabetes Association.
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| 45.
論文 |
論文
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Takahashi, D. ; Abe, Satoshi ; Mizuno, H. ; Tayurskii, Dmitrii A. ; Matsumoto, K. ; Suzuki, Haruhiko ; Onuki, Yoshichika
概要:
金沢大学大学院自然科学研究科物理学<br />金沢大学理学部<br />The magnetic properties of CeRu2Si2 at microkelvin temperatures (down to 170 μK) and
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ultrasmall magnetic fields (0.02∼6.21 mT) are investigated experimentally. The simultaneously measured ac susceptibility and static magnetization show neither evidence of the magnetic ordering, superconductivity down to the lowest temperatures nor conventional Landau Fermi-Liquid behavior. The results imply the magnetic transition temperature in undoped CeRu2Si2 is very close to absolute 0 K. The possibility for proximity of CeRu2Si2 to the quantum critical point without any doping is discussed.
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| 46.
論文 |
論文
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Oshima, Masanobu ; Oshima, Hiroko ; Taketo, Makoto Mark
概要:
金沢大学がん研究所<br />Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin biosynthesis, is induced by various st
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imuli including mechanical stress and plays important roles in pathophysiological conditions. For example, gravitational stress has been shown to induce expression of COX-2 in bone tissues, which is essential for bone homeostasis. To investigate whether COX-2 is induced by gravitational loading in other tissues than bone, we exposed mice to hypergravity at 2G and 3G for 4 h. We demonstrate here that COX-2 is induced in the mouse heart vessels by hypergravity. Moreover, hypoxia-inducible factor (HIF)-1α and its downstream genes such as inducible nitric oxide synthase, vascular endothelial growth factor, and heme oxygenase-1 were induced in the heart simultaneously, while none of these genes were induced in the COX-2(−/−) mouse heart. Therefore, COX-2 induced in the heart helps protect the heart function against hypoxia under hypergravity condition through HIF-1α induction.
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| 47.
図書 |
図書
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47. Primes of the form x[2] + ny[2] : Fermat, class field theory, and complex multiplication. 2nd ed
David A. Cox
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| 48.
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論文
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Takakura, Hisashi ; Furuichi, Yasuro ; Yamada, Tatsuya ; Jue, Thomas ; Ojino, Minoru ; Hashimoto, Takeshi ; Iwase, Satoshi ; Hojo, Tatsuya ; Izawa, Tetsuya ; Masuda, Kazumi
概要:
At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intra
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cellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min x 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the mVO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle. © 2015, Nature Publishing Group. All rights reserved.
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| 49.
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論文
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Kudo, Tomoya ; Takino, Takahisa ; Miyamori, Hisashi ; Thompson, Erik W. ; Sato, Hiroshi
概要:
金沢大学がん研究所がん病態制御<br />Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of m
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atrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation. © 2007 Japanese Cancer Association.
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| 50.
論文 |
論文
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Kikuchi, Akihiro ; Takayama, Hiroaki ; Tsugane, Hirohiko ; Shiba, Kazuhiro ; Chikamoto, Keita ; Yamamoto, Tatsuya ; Matsugo, Seiichi ; Ishii, Kiyoaki ; Misu, Hirofumi ; Takamura, Toshinari ; 菊地, 晶裕 ; 柴, 和弘 ; 松郷, 誠一 ; 石井, 清朗 ; 御簾, 博文 ; 篁, 俊成
概要:
金沢大学疾患モデル総合研究センター<br />Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine that causes skeletal muscle insulin r
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esistance. The circulating levels of LECT2 are a possible biomarker that can predict weight cycling because they reflect liver fat and precede the onset of weight loss or gain. Herein, to clarify the dynamics of this rapid change in serum LECT2 levels, we investigated the in vivo kinetics of LECT2, including its plasma half-life and tissue distribution, by injecting 125I-labelled LECT2 into ICR mice and radioactivity tracing. The injected LECT2 was eliminated from the bloodstream within 10 min (approximate half-life, 5 min). In the kidneys, the radioactivity accumulated within 10 min after injection and declined thereafter. Conversely, the radioactivity in urine increased after 30 min of injection, indicating that LECT2 is mainly excreted by the kidneys into the urine. Finally, LECT2 accumulated in the skeletal muscle and liver until 30 min and 2 min after injection, respectively. LECT2 accumulation was not observed in the adipose tissue. These findings are in agreement with LECT2 action on the skeletal muscle. The present study indicates that LECT2 is a rapid-turnover protein, which renders the circulating level of LECT2 a useful rapid-response biomarker to predict body weight alterations. © 2020, The Author(s).<br />CC-BY 4.0
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