Hydrogen sulfide inhibits activity of three isoforms of recombinant nitric oxide synthase.
To clarify the presence of cross-talk between H(2)S and NO, we investigated effect of NaHS, an H(2)S donor, on activity of recombinant NO synthase (NOS) isoforms. Activity of all nNOS, iNOS and eNOS was inhibited by NaHS (IC(50): 0.13-0.21 mM). In contrast, Na(2)SO(3), L-cysteine and threo-1,4-dimercapto-2,3-butanediol, a reductant, exerted poor inhibition of NOS activity. Increasing concentrations of tetrahydrobiopterin (BH(4)) reversed the NaHS inhibition of nNOS and eNOS, but not iNOS. Our data thus demonstrate inhibition of three NOS isoforms by NaHS/H(2)S, and suggest involvement of interaction of NaHS/H(2)S with BH(4) in inhibition of nNOS and eNOS, but not iNOS.
Kubo
Satoko
S
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
Kurokawa
Yuko
Y
Doe
Ichiko
I
Masuko
Takashi
T
Sekiguchi
Fumiko
F
Kawabata
Atsufumi
A
D000393:Air Pollutants / Q000633:toxicity*; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D003545:Cysteine / Q000633:toxicity; D004229:Dithiothreitol / Q000633:toxicity; D004791:Enzyme Inhibitors; D006801:Humans; D006862:Hydrogen Sulfide / Q000633:toxicity*; D009249:NADP / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D013431:Sulfates / Q000633:toxicity
D000393:Air Pollutants; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013431:Sulfates; C012036:sodium sulfate; D001708:Biopterins; D009249:NADP; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D003545:Cysteine; D004229:Dithiothreitol; D006862:Hydrogen Sulfide