Tauroursodeoxycholic Acid Prevents Glycochenodeoxycholic Acid-induced Apoptosis

Abstract

The hydrophilic bile salt tauroursodeoxycholic acid (TUDCA) is a potent inhibitor of apoptosis. The aim of this study was to determine the mechanism of the protective effect of TUDCA against the apoptosis induced by glycochenodeoxycholic acid (GCDCA) in rat hepatocytes (RLN-8 cells) . RLN-8 cells were treated with GCDCA and TUDCA. Expression of Fas, Bax α and Bcl-2 genes was detected by RT-PCR. The level of mitochondrial cytochrome C released into the cytosol, and the degree of caspase activity (caspase-3, -8 and -9) was determined. GCDCA increased the expression of mitochondrial-associated Bax α and caused release of cytochrome C, subsequently inducing apoptosis. Co-treatment with TUDCA significantly increased the viability of cells, compared with GCDCA alone. Co-incubation of TUDCA with GCDCA increased the expression of Bcl-2 and significantly inhibited the release of cytochrome C from mitochondria into the cytosol. TUDCA also inhibited activation of caspase-9 and caspase-3 in GCDCA-induced apoptotic cells. These results suggest that the effects of TUDCA are due to the increase in the mRNA levels of Bcl-2 which acts as an anti-apoptotic factor that sequentially prevents the release of cytochrome C from mitochondria and inhibits the activation of caspase-9 and caspase-3.