Regina Brigelius-Flohé1, Matilde Maiorino. 1. Department of Biochemistry of Micronutrients, German Institute of Human Nutrition, Nuthetal, Germany. flohe@dife.de
Abstract
BACKGROUND: 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. SCOPE OF THE REVIEW: Since GPxs have recently been reviewed under various aspects, we here focus on novel findings considering their diverse physiological roles exceeding an antioxidant activity. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
BACKGROUND: 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. SCOPE OF THE REVIEW: Since GPxs have recently been reviewed under various aspects, we here focus on novel findings considering their diverse physiological roles exceeding an antioxidant activity. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
Authors: Vishnu Hosur; Lisa M Burzenski; Timothy M Stearns; Michelle L Farley; John P Sundberg; Michael V Wiles; Leonard D Shultz Journal: Exp Mol Pathol Date: 2017-03-06 Impact factor: 3.362
Authors: Andrew M Lamade; Tamil S Anthonymuthu; Zachary E Hier; Yuan Gao; Valerian E Kagan; Hülya Bayır Journal: Exp Neurol Date: 2020-04-11 Impact factor: 5.330
Authors: Kai Hu; Lin Feng; Weidan Jiang; Yang Liu; Jun Jiang; Shuhong Li; Xiaoqiu Zhou Journal: Fish Physiol Biochem Date: 2014-04-29 Impact factor: 2.794
Authors: Wan Seok Yang; Rohitha SriRamaratnam; Matthew E Welsch; Kenichi Shimada; Rachid Skouta; Vasanthi S Viswanathan; Jaime H Cheah; Paul A Clemons; Alykhan F Shamji; Clary B Clish; Lewis M Brown; Albert W Girotti; Virginia W Cornish; Stuart L Schreiber; Brent R Stockwell Journal: Cell Date: 2014-01-16 Impact factor: 41.582