Lead induces Siberian tiger fibroblast apoptosis by interfering with intracellular homeostasis

文献类型： 外文期刊

第一作者： Liu, Zheng

作者： Liu, Zheng;Wang, Hui;Guo, Xuesong;Zhang, Wenxiu;Yuan, Ziao;Yuan, Hongyi;Liu, Xueting;Guan, Weijun;Zhang, Minghai

作者机构：

关键词： Siberian tiger;lead;apoptosis;fibroblasts

期刊名称：DRUG AND CHEMICAL TOXICOLOGY （ 影响因子：3.356； 五年影响因子：2.604 ）

ISSN： 0148-0545

年卷期： 2018 年 41 卷 2 期

页码：

收录情况： SCI

摘要： Lead (Pb2+) is a poisonous heavy metal that causes many pathophysiological effects in living systems. Its toxicological effects are well known as it causes apoptosis of several cell types and tissues. This study aimed to determine the criteria required for early diagnosis of Pb2+ poisoning in the Siberian tiger using a tiger population in China, to identify a safety Pb2+ concentration threshold, and to provide suggestions for preventing Pb2+ poisoning in Siberian tigers. We investigated the apoptotic effects of Pb2+ (0, 32, 64, and 125 mu M) for 12-48h on Siberian tiger fibroblasts in vitro. Typical apoptotic effects were observed after Pb2+ exposure. Pb2+ strongly blocked DNA synthesis in the G0/G1 phase and induced cell apoptosis in a dose- and time-dependent manner. Intracellular free calcium (Ca2+) levels, reactive oxygen species levels, and efflux of extracellular Ca2+ were increased. The mitochondrial membrane potential was lowered. Caspase-3, -8, and -9 activities were increased when fibroblasts were treated with 32, 64, and 125M Pb2+. The gene expression levels of Bax, caspase-3, -8, Fas, and p53 were increased, while that of Bcl-2 was decreased. Calcium homeostasis and mitochondrial function were disturbed. Ca2+ efflux, oxidative damage, activation of caspases, and regulation of Bax, Bcl-2, caspase-3, -8, Fas, and p53 gene expression played an important role in the apoptotic effects. The disorder of intracellular homeostasis was the trigger for apoptosis in Siberian tiger fibroblasts.

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