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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family.
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Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family.

机译:锰通过调节Bcl-2家族蛋白的表达来激活大鼠星形胶质细胞中的线粒体凋亡途径。

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摘要

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-1 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.
机译:锰通过尚未完全了解的机制诱发导致锰的中枢神经系统损伤。长期暴露于锰会产生氧化应激并诱导线粒体通透性转变。在本研究中,我们表征了大鼠皮质星形胶质细胞中与锰毒性相关的凋亡细胞死亡机制,并证明(i)Mn处理靶向线粒体并诱导线粒体膜去极化,随后细胞色素c释放到细胞质中,(ii)Mn诱导两者效应子胱天蛋白酶3/7和6以及PARP-1的切割,(iii)Mn改变Bcl-2家族蛋白的细胞死亡/存活平衡,以促进星形胶质细胞的凋亡。我们的模型系统使用经过Mn处理的皮质大鼠星形胶质细胞将成为旨在阐明凋亡在锰中的作用的研究的良好工具。

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