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Marcus Conrad, Manuela Schneider, Alexander Seiler, Georg W. Bornkamm
The physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals
Keywords: glutathione peroxidase 4, lipid peroxidation, selenoprotein, spermatogenesis, thiol peroxidase
The redox enzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) has emerged as one of the most significant selenoenzymes in mammals, corroborated by early embryonic lethality of PHGPx null mice. PHGPx is one out of five selenium dependent glutathione peroxidases and the second glutathione peroxidase to be discovered in 1982. PHGPx takes a particular position within this family, for its peculiar structural and catalysing properties, its multifaceted roles during male gametogenesis and its necessity for early mouse development. Interestingly, mice devoid of endogenous glutathione die at the same embryonic stage as PHGPxdeficient mice compatible with the hypothesis that a similar phenotype of embryonic lethality may be provoked by PHGPx deficiency and lack of its reducing substrate glutathione. Various gain and loss of function approaches in mice have provided early insights into the physiological functions of PHGPx. These include a protective role for PHGPx in response to irradiation, increased resistance of transgenic PHGPx mice to liver damage induced by toxins, a putative role in various steps of embryogenesis, and its contribution to sperm chromatin condensation. The expression of three forms of PHGPx and early embryonic lethality call for more specific studies, like tissuespecific disruption of PHGPx, to precisely understand the contribution of PHGPx to mammalian physiology and under pathological conditions.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 2007
Pages: -