期刊
TOXICOLOGY AND INDUSTRIAL HEALTH
卷 24, 期 10, 页码 643-653出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0748233708100370
关键词
apoptosis; As2O3; Bcl-2 family; caspase; hepatocyte; HSP 70 and 90
资金
- Department of Biotechnology, Ministry of Science Technology
- UGC for the Research Fellowship
- Council of Scientific and Industrial Research for project [37(1179)/04/EMR-II]
In India, arsenic contamination in ground water is of immediate environmental concern affecting a large number of inhabitants in Kolkata. Arsenic is known to be one of the most toxic metalloids naturally occurring in the environment giving rise to severe toxic manifestations including cancer. Because arsenic is also used in chemotherapy of leukemia, it was considered worthwhile to concentrate on the mechanism of toxic action in normal hepatocytes which has not been addressed earlier. Rat hepatocytes were isolated and incubated in As2O3 at concentrations of 10, 20, and 40 mu M in a time-dependent manner (0, 15, 30 min and 1, 2, and 4 h). The expression of the common stress proteins HSP 70 and 90 throughout the experimental duration confirmed the magnitude of toxic effect imposed by arsenic. Microscopic observations showed clear apoptotic changes in hepatocytes, which were further characterized by DNA ladder formation in time- and concentration-dependent manners. Apoptosis was triggered by caspase activation and over expression of bax at 10 mu M As2O3 and at 20 and 40 mu M concentrations of As2O3, MAP kinases were found to mediate the apoptotic pathway. Co-treatment of cells with arsenic and caspase inhibitor (Ac-DEVD-Cho) led to over expression of bcl-2, suppression of bax, and cytosolic sequestration of Bid and Bad. It is therefore concluded that caspase activation has a direct role in arsenic-induced apoptosis mediated by mitochondrial factors at 10 mu M As2O3, and JUN N-terminal kinase (JNK) and P38 activation are the major mediators of apoptosis at the higher test concentrations (20 and 40 mu M) of As2O3. Toxicology and Industrial Health 2008; 24: 643-653.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据