Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells.
Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells.
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DOI：
10.1016/j.taap.2010.03.004
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发表时间：
2010-06-01
影响因子：
3.8
通讯作者：
Shi X
中科院分区：
文献类型：
--
作者：
Son YO;Hitron JA;Wang X;Chang Q;Pan J;Zhang Z;Liu J;Wang S;Lee JC;Shi X
已知Cr（VI）化合物会引起严重的毒性和致癌作用。Cr（VI）暴露可导致严重的皮肤损伤，但Cr（VI）介导的皮肤毒性的机制尚不清楚。本研究探讨是否铬（VI）诱导细胞死亡的凋亡或坏死，使用小鼠皮肤表皮细胞系，JB6 Cl 41细胞。我们还研究了Cr（VI）诱导细胞死亡的细胞机制。这项研究表明，铬（VI）诱导凋亡细胞死亡的剂量依赖性的方式，表现为细胞皱缩的外观，迁移到亚G1期的细胞，增加Annexin V阳性染色的细胞，和核DNA梯状带的形成。Cr（VI）处理导致线粒体膜去极化和caspase激活增加。电子自旋共振（ESR）和荧光分析表明，铬（VI）的浓度依赖性的方式增加细胞内的活性氧（ROS），如过氧化氢和超氧阴离子自由基的水平。通过si-RNA转染阻断p53抑制了Bcl-2家族组成的线粒体变化、线粒体膜去极化、caspase激活和PARP切割，从而抑制Cr（VI）诱导的细胞凋亡。此外，过氧化氢酶处理阻止了由Cr（VI）刺激的p53磷酸化，同时抑制半胱天冬酶活化。这些结果表明，铬（VI）诱导的皮肤表皮细胞的p53，这主要是由化学产生的反应性氧化剂介导的激活，通过p53介导的细胞凋亡介导的和半胱天冬酶依赖的。
Cr(VI) compounds are known to cause serious toxic and carcinogenic effects. Cr(VI) exposure can lead to a severe damage to the skin, but the mechanisms involved in the Cr(VI)-mediated toxicity in the skin are unclear. The present study examined whether Cr(VI) induces cell death by apoptosis or necrosis using mouse skin epidermal cell line, JB6 Cl41 cells. We also investigated the cellular mechanisms of Cr(VI)-induced cell death. This study showed that Cr(VI) induced apoptotic cell death in a dose-dependent manner, as demonstrated by the appearance of cell shrinkage, the migration of cells into the sub-G1 phase, the increase of Annexin V-positively stained cells, and the formation of nuclear DNA ladders. Cr(VI) treatment resulted in the increases of mitochondrial membrane depolarization and caspases activation. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner. Blockage of p53 by si-RNA transfection suppressed mitochondrial changes of Bcl-2 family composition, mitochondrial membrane depolarization, caspase activation and PARP cleavage, leading to the inhibition of Cr(VI)-induced apoptosis. Further, catalase treatment prevented p53 phosphorylation stimulated by Cr(VI) with the concomitant inhibition of caspase activation. These results suggest that Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through activation of p53, which are mainly mediated by reactive oxidants generated by the chemical.
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影响因子：
7.4
作者：
Barbouti, A;Doulias, PT;Galaris, D
通讯作者：
Galaris, D
影响因子：
3.8
作者：
Hayashi, Y;Kondo, T;Kasuya, M
通讯作者：
Kasuya, M
影响因子：
7.4
作者：
Barbouti, Alexandra;Amorgianiotis, Christos;Galaris, Dimitrios
通讯作者：
Galaris, Dimitrios
影响因子：
3.5
作者：
Annunziato, L;Amoroso, S;Di Renzo, GF
通讯作者：
Di Renzo, GF
影响因子：
3.8
作者：
Flores, A;Pérez, JM
通讯作者：
Pérez, JM