Alleviation of Lead-Induced Apoptosis by Puerarin via Inhibiting Mitochondrial Permeability Transition Pore Opening in Primary Cultures of Rat Proximal Tubular Cells

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• 作者：Zhong-Kun Wang ; Xue-Lei Zhou ; Xiang-Bin Song…
• 关键词：Lead ; Apoptosis ; Mitochondria ; Puerarin ; Mitochondrial permeability transition ; Proximal tubular cells
• 刊名：Biological Trace Element Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：174
• 期：1
• 页码：166-176
• 全文大小：1,393 KB
• 刊物主题：Biochemistry, general; Biotechnology; Nutrition; Oncology;
• 出版者：Springer US
• ISSN：1559-0720
• 卷排序：174

文摘

Previous study has demonstrated that mitochondrial-dependent apoptotic pathway is involved in the nephroprotective effect of puerarin (PU) against lead-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. To further clarify how PU exerts its antiapoptotic effects, this study was designed to investigate the role of mitochondrial permeability transition (MPT) and subsequent apoptotic events in the process of PU against Pb-induced cytotoxicity in rPT cells. The results showed that Pb-mediated mitochondrial permeability transition pore (MPTP) opening together with mitochondrial cytochrome c release, activations of caspase-9 and caspase-3, and subsequent poly-ADP-ribose polymerase (PARP) cleavage can be effectively blocked by the addition of PU. Simultaneously, upregulation and downregulation of Bcl-2 and Bax with increased Bcl-2/Bax ratio due to PU administration further alleviated Pb-induced mitochondrial apoptosis. Moreover, PU can reverse Pb-induced ATP depletion by restoring mitochondrial fragmentation to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU produced a significant protection against Pb-induced mitochondrial apoptosis in rPT cells by inhibiting MPTP opening to ameliorate the mitochondrial dysfunction.