Metabolism of hydroperoxy-phospholipids in human hepatoma HepG2 cells.
Two enzymatic mechanisms have been proposed for the metabolism of hydroperoxy-phospholipids: i) the combined action of phospholipase A2 and glutathione peroxidase, and/or ii) direct enzymatic reduction. The latter reaction may be catalyzed by selenium-dependent phospholipid hydroperoxide glutathione peroxidase and/or by glutathione S-transferase alpha. To study the pathway of this reaction, we used human hepatoma HepG2 cells into which was incorporated labeled, hydroperoxy-phospholipids. The major product of incorporated l-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-L-3-phosphatidylcholine was the corresponding hydroxy-phospholipid with no hydroxy- or hydroperoxy-fatty acids. The contributions to reduction of hydroperoxy-phospholipids in HepG2 cells from glutathione S-transferase Al and phospholipid hydroperoxide glutathione peroxidase were calculated to be 0.5% and 99.5%, respectively. Increasing selenium in the cell culture medium led to increases in selenium-dependent phospholipid hydroperoxide glutathione peroxidase activity but not in glutathione S-transferase alpha. This increase in the selenium-dependent enzyme was paralleled by a concomitant increase in the extent of reduction of the incorporated hydroperoxy-phospholipid. We conclude that the main metabolic fate of hydroperoxy-phospholipids in HepG2 cells is by direct reduction to hydroxy-phospholipids by phospholipid hydroperoxide glutathione peroxidase but also by glutathione S-transferase alpha, and that phospholipase A2/selenium-dependent glutathione peroxidase does not play a significant role in the reduction.
Bao
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Department of Biochemistry, Institute of Food Research, Norwich Laboratory, Norwich Research Park, Colney, United Kingdom.
Williamson
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D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D014407:Tumor Cells, Cultured
D008054:Lipid Peroxides; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D010741:Phospholipases A; D054467:Phospholipases A2