金沢大学附属図書館 OPAC plus

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. 続きを見る

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 … 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. 続きを見る

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