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論文 |
論文
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Sugimoto, Naotoshi ; Miwa, Shinji ; Ohno-Shosaku, Takako ; Tsuchiya, Hiroyuki ; Hitomi, Yoshiaki ; Nakamura, Hiroyuki ; Tomita, Katsuro ; Yachie, Akihiro ; Koizumi, Shoichi
概要:
金沢大学医薬保健研究域医学系<br />During brain development, cAMP induces morphological changes and inhibits growth effects in several
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cell types. However, the molecular mechanisms underlying the growth inhibition remain unknown. Tumor suppressor protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that inhibits the phosphoinositide 3-kinase (PI3K) pathway. The phosphorylation of Akt, which is one of the key molecules downstream of PI3K, inhibits apoptosis. In this study, we investigated the role of PTEN in cAMP-mediated growth inhibition. B92 rat glial cells were treated with 2 different cAMP stimulatory agents, a phosphodiesterase (PDE) inhibitor and a β-adrenoceptor agonist. Both cAMP stimulatory agents induced marked morphological changes in the cells, decreased cell number, decreased Akt phosphorylation, activated PTEN, cleaved caspase-3, and induced the condensation and fragmentation of nuclei. These results indicate that the cAMP stimulatory agents induced apoptosis. Protein phosphatase inhibitor prevented cAMP-induced dephosphorylation of PTEN and Akt. In addition, cAMP analogs and Epac-selective agonists affected PTEN and Akt activities. These results suggested that cAMP-induced apoptosis may be mediated by PTEN activation and Akt inhibition through protein phosphatase in B92 cells. Our results provide new insight into the role of PTEN in cAMP-induced apoptosis in glial cells. © 2011 Elsevier Ireland Ltd.
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論文 |
論文
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Miwa, Shinji ; Sugimoto, Naotoshi ; Shirai, Toshiharu ; Hayashi, Katsuhiro ; Nishida, Hideji ; Ohnari, Issei ; Takeuchi, Akihiko ; Yachie, Akihiro ; Tsuchiya, Hiroyuki
概要:
金沢大学医薬保健研究域医学系<br />The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative re
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gulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activation exerts a strong anti-apoptotic effect and inhibits key pro-apoptotic proteins. We investigated the effect of caffeine in the prevention of tumor cell proliferation and induction of cell death. We found that caffeine induced increased intracellular cAMP levels, PTEN activation and Akt inactivation, which together prevented proliferation of human osteosarcoma cells (MG63) and fibrosarcoma cells (HT1080). PTEN knockdown by siRNA reduced the effects of caffeine on Akt inactivation in osteosarcoma cells. These results indicate that the tumor suppressor PTEN signaling pathway contributes to the growth-inhibitory effect of caffeine on sarcoma cells. Our data suggest that caffeine and other drugs that act on this pathway could have promising therapeutic effects in the treatment of sarcoma patients.
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