The Cytoprotective Role of Telomerase

• Main Authors: Jiun-Shiang Liau, 廖俊翔
• Other Authors: Yen-Chou Chen
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/36614747966156328698

碩士 === 臺北醫學大學 === 生藥學研究所 === 95 === We investigated the role of telomerase activation in platelet-derived growth factor (PDGF)- and fibroblast growth factor (FGF)-induced biological effects in NIH3T3 cells. Results of Telomeric repeat amplify- cation protocol (TRAP) showed that PDGF and FGF induced cellular proliferation in accordance with stimulated telomerase activity and COX-2 protein expression in NIH3T3 cells. Blockage of telomerase activity by telomerase inhibitor (TI) significantly reduced the proliferation induced by PDGF or FGF. Activation of ERKs and JNKs via increase in their protein phosphorylation which could be detect in PDGF- and EGF-treated NIH3T3 cells, and incubation of NIH3T3 cells with ERKs inhibitor PD98059 or JNKs inhibitor SP600125 significantly reduced PDGF- and FGF-induced telomerase activity and COX-2 protein expression with inhibiting cellular proliferation. Interestingly, telomerase activity induced by PDGF and FGF is inhibited by COX inhibitor NS398, and PGE2 treatment concentration-dependently induced telomerase activity in NIH3T3 cells. Furthermore, PDGF and FGF protection of NIH3T3 cells from C2 -ceramide-induced apoptosis through telomerase induction was demonstrated in the present study. These data suggest that telomerase activation is an important event in the proliferative and anti-apoptotic effect of PDGF and FGF, and induction of intracellular kinase cascades followed by activation of COX-2 gene expression and PGE2 production is involved.