Open AccessHydroxyl radical participation in the in vitro effects of Gram-negative endotoxin on cardiac sarcolemmal Na,K-ATPase activity.
Author(s) -
Ryusei Taga,
Eiichiro Okabe
Publication year - 1991
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.55.339
Subject(s) - chemistry , hydroxyl radical , superoxide dismutase , catalase , radical , superoxide , malondialdehyde , deferoxamine , hydrogen peroxide , nitric oxide , atpase , dimethyl sulfoxide , scavenger , lipid peroxidation , submitochondrial particle , biochemistry , reactive oxygen species , free radical scavenger , antioxidant , membrane , enzyme , organic chemistry
The effect of in vitro exposure of sarcolemmal membrane (SL) vesicles to Gram-negative endotoxin lipopolysaccharides (LPS) was studied. LPS decreased the Na,K-ATPase activity of SL vesicles; this effect was inhibited by hydroxyl radical (.OH) scavengers such as dimethylthiourea and dimethyl sulfoxide, but not by superoxide dismutase, a scavenger of superoxide anion radicals or by the hydrogen peroxide scavenger catalase. ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide verified the generation of .OH from LPS itself under the conditions used; .OH generated from LPS was not affected by deferoxamine, a powerful iron chelator. The Na,K-ATPase activity was reduced by an .OH radical generating system consisting of dihydroxyfumarate and Fe3(+)-ADP. Furthermore, exposure of SL vesicles to LPS caused an increase in malondialdehyde formation. It can be concluded that LPS damages cardiac SL by an oxygen free radical mechanism by the generation of .OH, due to inhibition of Na,K-ATPase activity and peroxidation of lipids, and that the effect of LPS is not dependent on the presence of contaminating iron.