Antioxidant defense against anthracycline cardiotoxicity by metallothionein.
Antioxidant defense against anthracycline cardiotoxicity by metallothionein.
复制标题
金属硫蛋白对蒽环类心脏毒性的抗氧化防御。
DOI：
10.1007/s12012-007-0007-3
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发表时间：
2007
影响因子：
3.2
通讯作者：
Kang,YJames
中科院分区：
文献类型：
--
作者：
Kang,YJames
蒽环类药物的心脏毒性与其在心脏中的代谢所产生的氧化应激有关。使用具有高水平抗氧化剂如过氧化氢酶或金属硫蛋白(MT)的转基因小鼠进行的研究表明，心脏抗氧化防御能力的提高导致了对蒽环类药物心脏毒性的干预。MT对蒽环类药物心脏毒性的保护作用与其通过抑制p38-MAPK和线粒体细胞色素c释放介导的细胞凋亡信号的抗凋亡作用有关。MT的抗细胞凋亡作用与其抗氧化作用密切相关，抗氧化作用涉及MT氧化还原循环调节锌的动态平衡。MT通过至少部分地通过锌的释放和锌从MT直接转移到受体蛋白来干扰氧化剂介导的有害过程。此外，MT还在翻译后调节与线粒体呼吸和能量代谢有关的关键蛋白。所有这些过程构成了MT保护蒽环类药物心脏毒性的机制。
Anthracycline cardiotoxicity is related to oxidative stress generated from the metabolism of anthracyclines in the heart. Studies using transgenic mice with high levels of antioxidants such as catalase or metallothionein (MT) specifically in the heart have demonstrated that elevation of cardiac antioxidant defense leads to intervention of anthracycline cardiotoxicity. MT protection against anthracycline-induced cardiac toxicity is related to its anti-apoptotic effect by inhibiting both p38-MAPK-mediated and mitochondrial cytochrome c-release-mediated apoptotic signaling. The anti-apoptotic effect of MT is closely related to its antioxidant action, which involves regulation of zinc homeostasis by the MT redox cycle. MT interferes with oxidant-mediated detrimental process through at least in part zinc release and zinc transfers directly from MT to acceptor proteins. In addition, MT posttranslationally modulates critical proteins involved in mitochondrial respiration and energy metabolism. All of these processes constitute the mechanisms by which MT protects from anthracycline cardiotoxicity.