Concomitant production of nitric oxide and superoxide in human macrophages.
Many harmful effects of nitric oxide are caused by the reaction of NO with superoxide anion. The present study was carried out to find out the concomitant production of superoxide and to investigate a suitable inhibitor of NO, which is produced by iNOS. THP-1 cells were differentiated into macrophages by PMA and cytokine. Addition of L-NAME showed decrement in superoxide production. Addition of apocynin, aminoguanidine or ONO 1714 brought about a significant reduction in superoxide production. The expressions of p67 and p47(phox) were reduced by the addition of apocynin, aminoguanidine or ONO 1714 whereas xanthine oxidase and cyclooxygenase did not have a major role in superoxide production. The results of the present study show that iNOS and NADPH oxidase play an important role in superoxide release. It suggests that addition of iNOS inhibitor together with apocynin may be more effective in case of therapeutic application in disease conditions like atherosclerosis.
Juliet
Packiasamy A R
PA
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, 466 8550 Nagoya, Japan.
Hayashi
Toshio
T
Iguchi
Akihisa
A
Ignarro
Louis J
LJ
D000098:Acetophenones / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
C407360:7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane; D000098:Acetophenones; D000578:Amidines; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006146:Guanidines; D006574:Heterocyclic Compounds, 2-Ring; D013481:Superoxides; D009569:Nitric Oxide; D000493:Allopurinol; C056165:acetovanillone; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D001241:Aspirin; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester