Abstract:
:Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is known about the effects of cholesterol oxidation on ion transport in isolated myocardial membranes. The purpose of the present study was to investigate the effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+ flux. Cholesterol oxidase was used to oxidatively modify membrane cholesterol. After incubation of cardiac sarcolemmal vesicles with cholesterol oxidase, cholest-4-en-3-one (cholestenone) was the predominant species of oxidated cholesterol produced. Cholesterol oxidase inhibited sarcolemmal Na(+)-Ca2+ exchange in a concentration-dependent manner. Both the Vmax and Km of the reaction were altered after cholesterol oxidase treatment. Extensive treatment of the sarcolemmal membranes with cholesterol oxidase increased the passive permeability characteristics of the membrane. Passive Ca2+ efflux from the sarcolemmal vesicles was stimulated by increasing the concentration of cholesterol oxidase. ATP-dependent Ca2+ uptake was also inhibited after cholesterol oxidase treatment, but it was not as sensitive as the Na(+)-Ca2+ exchange. Conversely, passive Ca2+ binding to sarcolemmal vesicles was strikingly stimulated by cholesterol oxidase treatment. The results demonstrate that oxidative modification of sarcolemmal membrane cholesterol can directly affect ionic interactions with the sarcolemmal vesicle and provide potentially important mechanistic information for the molecular basis of the effects of free radicals on ion flux and function in the heart.
journal_name
Circ Resjournal_title
Circulation researchauthors
Kutryk MJ,Maddaford TG,Ramjiawan B,Pierce GNdoi
10.1161/01.res.68.1.18subject
Has Abstractpub_date
1991-01-01 00:00:00pages
18-26issue
1eissn
0009-7330issn
1524-4571journal_volume
68pub_type
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