The peroxidase activity of mitochondrial superoxide dismutase.
The peroxidase activity of mitochondrial superoxide dismutase.
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DOI：
10.1016/j.freeradbiomed.2012.08.573
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发表时间：
2013-01
影响因子：
7.4
通讯作者：
Bonini, Marcelo G.
中科院分区：
文献类型：
--
作者：
Ansenberger-Fricano, Kristine;Ganini, Douglas;Mao, Mao;Chatterjee, Saurabh;Dallas, Shannon;Mason, Ronald P.;Stadler, Krisztian;Santos, Janine H.;Bonini, Marcelo G.
锰超氧化物歧化酶（MnSOD）是一种线粒体蛋白质，是对抗电子传递链副产物超氧阴离子自由基的第一线抗氧化剂。最近的研究已经形成了这样的想法，即通过调节线粒体氧化还原状态和H2O2流出，MnSOD作为细胞增殖，代谢和凋亡的基本调节剂，从而承担远远超出其拟议的抗氧化功能的作用。因此，MnSOD的等位基因变异已被证明增加线粒体中MnSOD的水平，导致前列腺癌风险增加10倍。此外，流行病学研究表明，还原型谷胱甘肽过氧化物酶（GPx）活性沿着H2O2的增加进一步增加了MnSOD过表达的癌症风险。这些事实使我们假设，像铜，锌对应物一样，MnSOD可能作为过氧化物酶发挥作用，利用H2O2促进线粒体损伤，这是一种已知的癌症风险因素。在这里，我们报告说，MnSOD确实具有过氧化物酶的活性，表现在线粒体中的酶被过度表达时。
Manganese superoxide dismutase (MnSOD) is an integral mitochondrial protein known as a first line antioxidant defense against superoxide radical anions produced as by-products of the electron transport chain. Recent studies have shaped the idea that by regulating the mitochondrial redox status and H2O2 outflow, MnSOD acts as a fundamental regulator of cellular proliferation, metabolism and apoptosis thereby assuming roles that extend far beyond its proposed antioxidant functions. Accordingly, allelic variations of MnSOD that have been shown to augment levels of MnSOD in mitochondria result in a 10-fold increase in prostate cancer risk. In addition, epidemiologic studies indicate that reduced glutathione peroxidase (GPx) activity along with increases in H2O2 further increase cancer risk in the face MnSOD overexpression. These facts led us to hypothesize that, like the Cu, Zn-counterpart, MnSOD may work as a peroxidase, utilizing H2O2 to promote mitochondrial damage, a known cancer risk factor. Here we report that MnSOD indeed possesses peroxidase activity that manifests in mitochondria when the enzyme is overexpressed.
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