Dynamic and biphasic modulation of nitrosation reaction by superoxide dismutases.
It has been shown that superoxide dismutase (SOD) can both potentiate and attenuate NO-mediated toxicity. This present study investigated the role of SOD and GSH in a sustained nitrosative and oxidative environment simulated by the nitric oxide (NO) and superoxide (O(2)(.-)) donor, 3-morpholinosydnonimine (SIN-1). We describe, for the first time, that SOD modulates nitrosative chemistry in a dynamic fashion that is both concentration and time-dependent. Specifically, our results show that SOD's effects on nitrosation are biphasic in nature i.e., while lower concentrations of SOD are pronitrosative, higher SOD concentrations inhibit nitrosation. However, even those initially inhibitory higher SOD concentrations became pronitrosative over time. In the presence of physiologically relevant levels of GSH, SOD predominantly exhibits a pronitrosative effect, with a complete loss of antinitrosative effects noted at higher levels of GSH. Our findings likely reflect the complex and dynamic nature of SOD interactions with oxidative and nitrosative species.
Hu
Teh-Min
TM
Division of Pharmaceutics, College of Pharmacy, Columbus, OH 43210-1241, USA.
Hayton
William L
WL
Morse
Mark A
MA
Mallery
Susan R
SR
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism; D010084:Oxidation-Reduction; D012235:Rhodamines / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D012235:Rhodamines; D029701:Saccharomyces cerevisiae Proteins; C058319:dihydrorhodamine 123; C026373:2,3-diaminonaphthalene; D009569:Nitric Oxide; C069938:SPT2 protein, S cerevisiae; D015081:2-Naphthylamine; D013482:Superoxide Dismutase; D005978:Glutathione