Oxidant stress enhances Lyso-PAF-AcT activity by modifying phospholipase D and phosphatidic acid in aortic endothelial cells.
Oxidant stress, as a consequence of selenium (Se) deficiency, alters production of vasoactive compounds including platelet-activating factor (PAF). Recent studies report that enhanced PAF production during Se deficiency is a consequence of increased lyso-PAF:acetyl-coenzyme A acetyltransferase (Lyso-PAF-AcT) activity. To elucidate the mechanism behind increased Lyso-PAF-AcT activity during oxidant stress, phospholipase D (PLD) activity and phosphatidic acid (PA) production were examined. Increased PLD activity and PA production were exhibited in bovine aortic endothelial cells using a Se-deficient model of oxidant stress. The direct effects of PLD and PA on Lyso-PAF-AcT activity were assessed using selective inhibitors and repletion experiments. Following the inhibition of PLD and addition of exogenous PA, Lyso-PAF-AcT activity significantly decreased and increased, respectively. Therefore, Se deficiency enhances Lyso-PAF-AcT activity in part by modifying PLD and PA. This suggests a novel link between Se status and PAF production, providing potential upstream therapeutic targets for PAF regulation under conditions of oxidant stress.
Corl
C M
CM
Department of Veterinary Science, The Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA.
Cao
Y Z
YZ
Cohen
Z S
ZS
Sordillo
L M
LM
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D018384:Oxidative Stress; D010712:Phosphatidic Acids / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism; D011485:Protein Binding; D017382:Reactive Oxygen Species; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D010712:Phosphatidic Acids; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D010739:Phospholipase D; D005978:Glutathione; D012643:Selenium