Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1992-10-8
pubmed:abstractText
Myocardial phospholipase D (PLD) is primarily localized at the sarcolemmal level and selectively hydrolyzes phosphatidylcholine to form phosphatidic acid as part of the signal transduction mechanisms for regulating Ca2+ movements in the heart. Since the myocardial cell damage induced by oxidative stress is associated with abnormalities in Ca2+ homeostasis and thiol status, we examined the thiol group dependence and the effects of oxidant species on this enzyme. Sarcolemmal membranes isolated from rat heart were exposed to several types of thiol group modifiers. Alkylation with N-ethylmaleimide or methyl methanethiosulfonate, mercaptide formation with p-chloromercuriphenylsulfonic acid, and thiol-disulfide exchange with 5,5'-dithio-bis(2-nitrobenzoate) depressed sarcolemmal PLD activity; in all cases the depression was prevented by dithiothreitol. At different concentrations of N-ethylmaleimide the PLD depression correlated well (r = 0.98) with the decrease in total thiol group content of the membrane. The enzyme activity was not affected by xanthine-xanthine oxidase, a superoxide anion-generating system, but was depressed by hydrogen peroxide (H2O2) in a concentration-dependent manner. This inhibitory effect was prevented by catalase as well as by dithiothreitol, but not by D-mannitol. The effect of a hydroxyl radical-generating system (Fenton reaction) could not be assessed because of an interfering direct inhibition by Fe2+. Dithiothreitol was also able to restore PLD activity in H2O2-pretreated membranes and to prevent a severe deactivation of the enzyme by hypochlorous acid (HOCI). Protection by glutathione and inhibition by its oxidized form were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0009-7330
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
970-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Depression of cardiac sarcolemmal phospholipase D activity by oxidant-induced thiol modification.
pubmed:affiliation
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't