Origin of superoxide production by endothelial nitric oxide synthase.
Using fluorescence optical and electron spin resonance spectroscopy, we have investigated the production of superoxide by bovine endothelial nitric oxide synthase (NOS). In contrast to neuronal NOS, the heme moiety is identified as the exclusive source of superoxide production by endothelial NOS. Thus, calmodulin-mediated enzyme regulation affects production of nitric oxide and superoxide simultaneously and inseparably. The balance between the nitric oxide/superoxide reaction pathways may be shifted by addition of exogenous heme-specific agents, such as tetrahydrobiopterin. Our results have direct relevance for the pathophysiology of atherosclerosis.
Stroes
E
E
Department of Nephrology and Vascular Medicine, F 03.226, University Hospital Utrecht, The Netherlands. e.stroes@digd.azu.nl
Hijmering
M
M
van Zandvoort
M
M
Wever
R
R
Rabelink
T J
TJ
van Faassen
E E
EE
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D004369:Pentetic Acid / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera; D013481:Superoxides / Q000378:metabolism*; D014162:Transfection
D011994:Recombinant Proteins; D013481:Superoxides; D009569:Nitric Oxide; D004369:Pentetic Acid; D004492:Edetic Acid; D002374:Catalase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester