Effects of oxidized low density lipoprotein on nitric oxide synthetase and protein kinase C activities in bovine endothelial cells.
Oxidized low-density lipoprotein (Ox-LDL) is an atherogenic lipoprotein. It has been suggested that Ox-LDL causes endothelial dysfunction by decreasing the release of endothelium-derived factors (EDRF-NO) or increasing the inactivation of EDRF-NO. The mechanism by which Ox-LDL causes dysfunctional NO during early stages of atherosclerosis is not clear. The purpose of this study was to examine the role of Ox-LDL on nitric oxide synthetase (eNOS), protein kinase C (PKC) activities and cAMP production in bovine aortic endothelial cells (BAEC). Ox-LDL stimulated PKC activity of BAEC but it inhibited both eNOS activity and cAMP production. Ox-LDL partially inhibited the forskolin stimulated cAMP production. Furthermore, we observed that 8Br-cAMP treatment decreased the activity of eNOS in a concentration dependent manner. Serotonin which has a profound inhibitory effect on cAMP production also stimulated eNOS activity. Pertusis toxin treatment blocked the stimulatory action of serotonin on the stimulation of eNOS activity. Our results thus suggest that Ox-LDL inhibit the endothelium-dependent relaxation. One possible mechanism is that Ox-LDL stimulates PKC activity, which in turn increases the phosphorylation of the Gi-protein. Inhibition of Gi-protein then leads to reduced release of NO from endothelial cells and thus causes endothelial dysfunction.
Mukherjee
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S
Dept of Biochemistry, Meharry Medical College, Nashville, TN 37208, USA. smukherjee@mmc.edu
Coaxum
S D
SD
Maleque
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M
Das
S K
SK
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005576:Colforsin; D012701:Serotonin; D002772:Cholera Toxin; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D007545:Isoproterenol