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Kim, Jung-Ae,Kang, Yoiung Shin,Lee, Sun Hee,Lee, Eun-Hee,Yoo, Byong Hoon,Lee, Yong Soo 영남대학교 약품개발연구소 1999 영남대학교 약품개발연구소 연구업적집 Vol.9 No.-
Glibenclamide, an inhibitor of cystic fibrosis trans-membrane conductance regulator (CFTR) Cl- chan-nels, induced apoptosis in a dose- and time-depen-dent manner in HepG2 human hepatoblastoma cells. Glibenclamide increased intracellular Ca^(2+) concentra-tion, which was significantly inhibited by Ca^(2+) release blockers dantrolene and TMB-8. BAPTA/AM, an intra-cellular Cn^(2+) chelator, and the Ca^(2+) release blockers significantly inhibited glibenclamide-induced apopto-sis. Glibanclamide also increased intracellular Cl-concentration, which wss significantly blocked by CFTR Cl- channel activators levamisole and bro-motetramisole. These activators also significantly in-hibited both intracellular Ca^(2+) release and apoptosis induced by glibenclamide. The expression of CTTR protein in the cells was confirmed by Western blot analysis. These results suggest that glibenclamide in-duced apoptosis through inhibition of CFTR Cl- chan-nels and intracellular Ca^(2+) release and that this pro-tein may be a good target for treatment of human hepatomas.