The mechanism of thioacetamide-induced apoptosis

• Main Authors: Li-Hsuen Chen, 陳立學
• Other Authors: Ching-Feng Weng
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/63036563686374932757

碩士 === 國立東華大學 === 生物技術研究所 === 91 === Thioacetamide（TAA）, a thio-sulfur-containing compound, which is a common inducer for studying the liver fibrosis and cirrhosis. Shortly after administration, it undergoes extensive metabolism and becomes the very oxy-reactive compound thioacetamide-S-dioxide, which causes liver-damaging and carcinogen. Numerous studies in rats indicated the involvement of oxidative stress in the etiology of TAA-induced liver damage. Oxidative stress is caused by exposure to reactive oxygen species（ROS，O2*-、OH*、H2O2）, which can affect the delecterious effect of proteins and cell membranes, even lead to necrosis and apoptosis. The mechanisms of TAA and ROS induced apoptosis are still unclear. Rat normal liver cell line-clone 9 was applied to study 1）could TAA cause liver cell death（apoptosis or necrosis）? 2）could TAA induce Oxidative stress？ 3）which pathway could be involved in TAA-induced apoptosis？ The results showed that TAA caused clone 9 cell death is dose-dependent manner, and 60﹪cell death within 24 hours was found after 100 mM TAA administration. Apoptotic cell percentage and Caspase 3 activity are the highest after 100 mM TAA administration at 8 hours. The release of GSH and elevation of Caspase after TAA-induced resulted the clone 9 cell apoptosis, which is via oxidative stress and Caspase-dependent mechanism. The phospho-p53, Bax and Bad protein expressions were elevated after TAA-induced clone 9 cell. Obviously, TAA could activate p53 and consequently increase Bax protein, which causes the release of cytochrome c from mitochondria and disintegration of membrane leading to apoptosis.