Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals

Marcus Conrad 1 , 1 , Manuela Schneider 2 , 2 , Alexander Seiler 3 , 3  and Georg W. Bornkamm 4 , 4
  • 1 Institute of Clinical Molecular Biology and Tumour Genetics, GSF-National Research Center for Environment and Health, Marchioninistr. 25, D-81377 Munich, Germany
  • 2 Institute of Clinical Molecular Biology and Tumour Genetics, GSF-National Research Center for Environment and Health, Marchioninistr. 25, D-81377 Munich, Germany and present address: Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität München, Marchioninistr. 15, D-81377 Munich, Germany
  • 3 Institute of Clinical Molecular Biology and Tumour Genetics, GSF-National Research Center for Environment and Health, Marchioninistr. 25, D-81377 Munich, Germany
  • 4 Institute of Clinical Molecular Biology and Tumour Genetics, GSF-National Research Center for Environment and Health, Marchioninistr. 25, D-81377 Munich, Germany

Abstract

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 of five selenium-dependent glutathione peroxidases and the second glutathione peroxidase to be discovered in 1982. PHGPx has a particular position within this family owing to its peculiar structural and catalytic 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 PHGPx-deficient 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 some 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 toxin-induced liver damage, a putative role in various steps of embryogenesis, and a contribution to sperm chromatin condensation. The expression of three forms of PHGPx and early embryonic lethality call for more specific studies, such as tissue-specific disruption of PHGPx, to precisely understand the contribution of PHGPx to mammalian physiology and under pathological conditions.

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Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.

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