Brigelius-Flohé Regina, Maiorino Matilde
Department of Biochemistry of Micronutrients, German Institute of Human Nutrition, Nuthetal, Germany.
Biochim Biophys Acta. 2013 May;1830(5):3289-303. doi: 10.1016/j.bbagen.2012.11.020. Epub 2012 Nov 29.
With increasing evidence that hydroperoxides are not only toxic but rather exert essential physiological functions, also hydroperoxide removing enzymes have to be re-viewed. In mammals, the peroxidases inter alia comprise the 8 glutathione peroxidases (GPx1-GPx8) so far identified.
Since GPxs have recently been reviewed under various aspects, we here focus on novel findings considering their diverse physiological roles exceeding an antioxidant activity.
GPxs are involved in balancing the H2O2 homeostasis in signalling cascades, e.g. in the insulin signalling pathway by GPx1; GPx2 plays a dual role in carcinogenesis depending on the mode of initiation and cancer stage; GPx3 is membrane associated possibly explaining a peroxidatic function despite low plasma concentrations of GSH; GPx4 has novel roles in the regulation of apoptosis and, together with GPx5, in male fertility. Functions of GPx6 are still unknown, and the proposed involvement of GPx7 and GPx8 in protein folding awaits elucidation.
Collectively, selenium-containing GPxs (GPx1-4 and 6) as well as their non-selenium congeners (GPx5, 7 and 8) became key players in important biological contexts far beyond the detoxification of hydroperoxides. This article is part of a Special Issue entitled Cellular functions of glutathione.
越来越多的证据表明，氢过氧化物不仅具有毒性，而且还发挥着重要的生理功能，因此对氢过氧化物清除酶也需要重新审视。在哺乳动物中，过氧化物酶尤其包括迄今为止已鉴定出的8种谷胱甘肽过氧化物酶（GPx1 - GPx8）。
由于最近已经从各个方面对谷胱甘肽过氧化物酶进行了综述，我们在此重点关注考虑到其超出抗氧化活性的多种生理作用的新发现。
谷胱甘肽过氧化物酶参与平衡信号级联反应中的过氧化氢稳态，例如通过GPx1参与胰岛素信号通路；GPx2在癌症发生过程中根据起始模式和癌症阶段发挥双重作用；GPx3与膜相关，这可能解释了尽管血浆中谷胱甘肽浓度较低但其仍具有过氧化物酶功能；GPx4在细胞凋亡调节中具有新作用，并且与GPx5一起在男性生育中发挥作用。GPx6的功能仍然未知，并且关于GPx7和GPx8参与蛋白质折叠的推测有待阐明。
总的来说，含硒的谷胱甘肽过氧化物酶（GPx1 - 4和6）及其非硒同类物（GPx5、7和8）在远远超出氢过氧化物解毒的重要生物学背景中成为关键参与者。本文是名为“谷胱甘肽的细胞功能”的特刊的一部分。
