Arsenate-induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial-mediated oxidative injury.
Arsenate-induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial-mediated oxidative injury.
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DOI：
10.1002/bdra.20623
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发表时间：
2010-01
影响因子：
--
通讯作者：
Pisano, M. Michele
中科院分区：
文献类型：
--
作者：
Singh, Saurabh;Greene, Robert M.;Pisano, M. Michele
砷是一种普遍存在的元素，是一种潜在的致癌物和致畸物，可导致不利的发育结果。砷通过产生活性氧（ROS）来发挥其毒性作用，活性氧包括过氧化氢（H2O2）、超氧衍生的羟基离子和过氧自由基。然而，砷诱导小鼠胚胎上颌间充质（MEMM）细胞毒性的分子机制尚不清楚。用不同浓度的五价砷酸钠[As (V)]处理培养的MEMM细胞24或48小时，并测量不同终点。我们发现，用五价形式的无机砷处理MEMM细胞导致caspase介导的凋亡，伴随着ROS的产生和线粒体膜电位的破坏。caspase抑制剂明显阻断细胞凋亡。此外，自由基清除剂n -乙酰半胱氨酸显著减弱砷介导的ROS生成和凋亡，砷酸盐暴露增加MEMM细胞中的Bax和降低Bcl蛋白水平。综上所述，这些发现表明，在MEMM细胞中，砷酸盐介导的氧化损伤是细胞死亡级联的早期和上游启动器，引发细胞毒性、线粒体功能障碍、Bcl/Bax蛋白比例改变和caspase-9的激活。
Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can cause adverse developmental outcomes. Arsenic exerts its toxic effects through the generation of reactive oxygen species (ROS) that include hydrogen peroxide (H2O2), superoxide-derived hydroxyl ion, and peroxyl radicals. However, the molecular mechanisms by which arsenic induces cytotoxicity in murine embryonic maxillary mesenchymal (MEMM) cells are undefined. MEMM cells in culture were treated with different concentrations of pentavalent sodium arsenate [As (V)] for 24 or 48 hours and various end points measured. We show that treatment of MEMM cells with the pentavalent form of inorganic arsenic resulted in caspase-mediated apoptosis, accompanied by generation of ROS and disruption of mitochondrial membrane potential. Treatment with caspase inhibitors markedly blocked apoptosis. In addition, the free radical scavenger N-acetylcysteine dramatically attenuated arsenic-mediated ROS production and apoptosis, and exposure to arsenate increased Bax and decreased Bcl protein levels in MEMM cells. Taken together, these findings suggest that in MEMM cells, arsenate-mediated oxidative injury acts as an early and upstream initiator of the cell death cascade, triggering cytotoxicity, mitochondrial dysfunction, altered Bcl/Bax protein ratios, and activation of caspase-9.
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影响因子：
4.1
作者：
Chen, PH;Lan, CCE;Chen, GS
通讯作者：
Chen, GS
影响因子：
8
作者：
Fulda, S;Meyer, E;Debatin, KM
通讯作者：
Debatin, KM
影响因子：
5.3
作者：
Lin, YT;Kokontis, J;Xiang, JL
通讯作者：
Xiang, JL
DOI：
10.1073/pnas.95.14.8103
发表时间：
1998-07-07
影响因子：
11.1
作者：
Hei, TK;Liu, SX;Waldren, C
通讯作者：
Waldren, C
影响因子：
3.5
作者：
Kowaltowski, AJ;Castilho, RF;Vercesi, AE
通讯作者：
Vercesi, AE