Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family
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DOI：
10.1016/j.neuint.2008.09.008
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发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Kotler, Monica L.
中科院分区：
文献类型：
--
作者：
Gonzalez, Laura E.;Juknat, A. Ana;Kotler, Monica L.
锰会引起中枢神经系统损伤，导致锰中毒，其机制尚不完全清楚。长期接触锰会产生氧化应激并诱导线粒体通透性转变。在本研究中，我们表征了与大鼠皮质星形胶质细胞中锰毒性相关的细胞凋亡机制，并证明（i）锰治疗以线粒体为目标，诱导线粒体膜去极化，然后将细胞色素c释放到细胞质中，（ii）锰诱导效应半胱天冬酶3/7和6以及PARP-I裂解，（iii）锰改变了Bcl-2家族蛋白的细胞死亡/存活的平衡有利于星形胶质细胞的凋亡。我们使用经锰处理的大鼠皮层星形胶质细胞的模型系统将成为旨在阐明细胞凋亡在锰中毒中的作用的研究的良好工具。 (C) 2008 Elsevier Ltd. 保留所有权利。
Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-I cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism. (C) 2008 Elsevier Ltd. All rights reserved.