A Novel Mechanism for Protecting of Biomembrane from Oxidative Disorder by Oxygen Free Radicals

点击翻译按钮获取中文摘要

Lipid peroxidation induced by oxygen free radicals in animal cells on tissues has long been strongly suggested to play an important role in aging, carcinogenesis, atherosclerosis, and so on in animal and human. The purpose of this research project is to study 1) the hepatic microsomal glutathione (GSH) S-transferase (GST) protecting the microsomal membrane from disorder caused by lipid peroxidation, 2) the hepatic cytosolic GST detoxifying fatty acid hydroperoxides enzymatically released from cellular membranes, and 3) the lipid peroxide as an endogenous marker in aging. The results of these studies are summarized below.1. A small molecular size (15 KDa) of GST was isolated and purified from rat liver microsomes and identified with the previously reported microsomal protein by N-terminal amino acid sequencing. The GST directly catalyzed the reduction of various phospholipid hydroperoxides in microsomes to the corresponding alcohols in the presence of GSH. It also reduced a variety of polyunsaturated fatty acid hydroperoxides and cholesterol 7-hydroperoxides (Ch 7-OOH). The enzymatic function of this GST as a GSH peroxidase has been little known.2. A new class of homodimeric GST, designated Yrs-Yrs, was found in rat liver cytosol. The new soluble GST was isolated and purified to homogeneity from the cytosol and found to have an extremely high activity as a GSH peroxidase toward various fatty acid hydroperoxides compared with all the known GSTs. Molecular cloning of a rat liver cDNA library indicated GST Yrs-Yrs to be expressed from an unknown gene family, named theta GST, in the rat.3. In rat skin, Ch 7-OOH existing as free and ester forms accumulate with linearlity upto an age of 45 weeks after birth. The extremely good relationship (r=0.874) observed between the dermal concentration of Ch 7-OOH and aging has never been reported with any other endogenous substance. Therefore, the author proposes Ch 7-OOH in rat skin to be a new good marker in aging.