Palmitate increases nitric oxide synthase activity that is involved in palmitate-induced cell death in cardiomyocytes.
The objective of this study was to test the hypothesis that nitric oxide synthase (NOS) is subjected to regulatory control by palmitate, and that nitric oxide (NO) is operative in palmitate-induced cell death. Palmitate induced a significant ( p<0.05 ) concentration-dependent increase in NOS activity measured by the conversion of [(3)H]arginine to [3H]citrulline in embryonic chick cardiomyocytes. Cellular eNOS and iNOS, determined by immunocytochemistry, were increased by palmitate. Western blotting also showed that palmitate, 500 microM for 4h, significantly increased the amount of cellular of eNOS and iNOS by 36.2+/-6.5% ( p<0.001 ) and 38.4+/-14.4% ( p<0.05 ), respectively. The NOS inhibitor L-NAME significantly ( p<0.05 ) accentuated palmitate-induced cell death These data suggest that palmitate has a bifunctional effect on cell viability--in addition to loss of cell viability, palmitate stimulates NOS activity by inducing an increase in cellular eNOS and iNOS with the resultant NO production serving to protect cardiomyocytes from palmitate-induced cell death.
Tsang
Michael Y C
MY
Department of Medicine, University of British Columbia, 2733 Heather St., Vancouver, BC, Canada V5Z 3J5.
Cowie
Scott E
SE
Rabkin
Simon W
SW
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002642:Chick Embryo; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019308:Palmitic Acid / Q000494:pharmacology*
D019308:Palmitic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester