Caspase-Dependent and Caspase-Independent Pathways Are Involved in Cadmium-Induced Apoptosis in Primary Rat Proximal Tubular Cell Culture.
Caspase-Dependent and Caspase-Independent Pathways Are Involved in Cadmium-Induced Apoptosis in Primary Rat Proximal Tubular Cell Culture.
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Caspase 依赖性和 Caspase 独立途径参与原代大鼠近端肾小管细胞培养中镉诱导的细胞凋亡
DOI：
10.1371/journal.pone.0166823
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Liu G;Zou H;Luo T;Long M;Bian J;Liu X;Gu J;Yuan Y;Song R;Wang Y;Zhu J;Liu Z
我们设计了这项研究，以探讨镉是否诱导caspase非依赖性凋亡，并探讨caspase依赖性和caspase非依赖性凋亡途径之间的关系。镉（1.25-2.5 μM）可诱导大鼠近端肾小管（rPT）细胞的氧化应激，如活性氧水平所示; N-乙酰半胱氨酸可防止这一点。环孢菌素A（CsA）阻止线粒体通透性转换孔开放和细胞凋亡;线粒体超微结构破坏，线粒体细胞色素c（cyt c）易位到细胞质，以及随后的caspase-9和caspase-3激活。Z-VAD-FMK可抑制caspase-3的活化和凋亡，降低BNIP-3（Bcl-2/腺病毒E1 B 19-kDa相互作用蛋白3）的表达水平和凋亡诱导因子/内切核酸酶G（AIF/Endo G）的转位。同时，镉诱导线粒体中BNIP-3的显著表达和细胞质AIF/Endo G易位到细胞核。BNIP-3沉默可显著抑制AIF和Endo G的易位，并降低细胞凋亡率、细胞色素c释放以及caspase-9和caspase-3的活化。这些结果表明，BNIP-3参与caspase-独立的凋亡途径，并位于AIF/Endo G的上游; caspase-依赖性和caspase-独立的途径都参与镉诱导的rPT细胞凋亡，并协同作用。
We designed this study to investigate whether cadmium induces caspase-independent apoptosis and to investigate the relationship between the caspase-dependent and caspase-independent apoptotic pathways. Cadmium (1.25–2.5 μM) induced oxidative stress in rat proximal tubular (rPT) cells, as seen in the reactive oxygen species levels; N-acetylcysteine prevented this. Cyclosporin A (CsA) prevented mitochondrial permeability transition pore opening and apoptosis; there was mitochondrial ultrastructural disruption, mitochondrial cytochrome c (cyt c) translocation to the cytoplasm, and subsequent caspase-9 and caspase-3 activation. Z-VAD-FMK prevented caspase-3 activation and apoptosis and decreased BNIP-3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) expression levels and apoptosis-inducing factor/endonuclease G (AIF/Endo G) translocation. Simultaneously, cadmium induced prominent BNIP-3 expression in the mitochondria and cytoplasmic AIF/Endo G translocation to the nucleus. BNIP-3 silencing significantly prevented AIF and Endo G translocation and decreased the apoptosis rate, cyt c release, and caspase-9 and caspase-3 activation. These results suggest that BNIP-3 is involved in the caspase-independent apoptotic pathway and is located upstream of AIF/Endo G; both the caspase-dependent and caspase-independent pathways are involved in cadmium-induced rPT cell apoptosis and act synergistically.
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DOI：
10.1023/b:jobb.0000041755.22613.8d
发表时间：
2004-08-01
影响因子：
3
作者：
Dawson, VL;Dawson, TM
通讯作者：
Dawson, TM
影响因子：
56.9
作者：
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10.1152/ajprenal.00276.2005
发表时间：
2006-10-01
影响因子：
4.2
作者：
Lee, Wing-Kee;Abouhamed, Marouan;Thevenod, Frank
通讯作者：
Thevenod, Frank
影响因子：
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作者：
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Kim, GW