Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol undergoes spontaneous autoxidation, leading to the production of potentially atherogenic oxidation derivatives. When 25-hydroxycholesterol (25-OH) or cholestane-3 beta, 5 alpha, 6 beta-triol (triol) was injected intravenously into rabbits, the aortic surfaces showed numerous balloon-like protrusions and crater-like defects indicative of endothelial damage. Alterations in membrane function caused by these cholesterol oxides could be the mechanism for their cytotoxic effect. Carrier-mediated hexose transport by cultured rabbit aortic smooth muscle cells, measured using 2-deoxyglucose, was reversibly inhibited by triol within one hour. A membrane-bound enzyme, 5'-nucleotidase, was inhibited after 24 to 48 hrs incubation with either 25-OH or triol. Endocytosis was also significantly inhibited by both 25-OH and triol. Depletion of membrane cholesterol content by the cholesterol oxides could account for the membrane functional alterations. Cholesterol biosynthesis is markedly inhibited by 25-OH. Triol has a lesser effect on cholesterol biosynthesis, but it is more potent in blocking uptake of cholesterol by arterial cells in culture. Cholesterol oxides may also influence cholesteryl ester accumulation by arterial smooth muscle cells. Incubation of cells with 25-OH resulted in a four-fold increase in cholesterol esterifying activity but no effect on cholesteryl ester hydrolytic activity. The cholesterol oxides appear to be transported in the blood primarily by very low density lipoproteins (VLDL) and low density lipoproteins (LDL). Oxidized LDL has cytotoxic effects and enhances macrophage lipid accumulation. These be effects may be directly related to the cholesterol oxide content of these lipoproteins.
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PMID:The role of cholesterol oxidation products in the pathogenesis of atherosclerosis. 266 53

Cholestane-3 beta, 5 alpha, 6 beta-triol and 25-hydroxycholesterol are two of the most cytotoxic and also relatively abundant of the autoxidation derivatives of cholesterol. Cultured aortic smooth muscle cells which were incubated with 10 micrograms/ml of either sterol for 24 to 48 hr showed a marked decrease of 5'-nucleotidase activity in isolated crude membranes. It was further demonstrated that 5'-nucleotidase activity was also markedly decreased in plasma membrane-enriched fractions when cells were incubated with cholestane-3 beta,5 alpha,6 beta-triol. Na+,K+-ATPase activity in crude membranes showed a significant decrease (32%) only in cells incubated with cholestane-3 beta,5 alpha,6 beta-triol for 48 hr. There was no effect on Na+,K+-ATPase activity in cells incubated for 24 hr with either sterol.
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PMID:Influence of cholesterol oxidation derivatives on membrane bound enzymes in cultured aortic smooth muscle cells. 299 76

Autoxidation derivatives of cholesterol known to affect cholesterol content of the cells were shown to alter some membrane associated functions in cultured aortic smooth muscle cells. For study of membrane-bound enzymes, Na+,K+-ATPase and 5'-nucleotidase were measured cytochemically by electron microscopy. Cells incubated with 10 ug/ml of cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol for 24 to 48 hours showed marked inhibition of both enzyme activities. For study of carrier-mediated hexose transport, radiolabeled 2-deoxy-D-glucose was utilized. The uptake of this labeled compound was measured in the cells preincubated with oxidation derivatives of cholesterol for various time periods. Cholestane-3 beta,5 alpha,6 beta-triol had a rapid inhibitory effect on hexose transport, which was reversible after removal of the sterol from the medium. Hexose transport was not significantly altered by 25-hydroxycholesterol after up to 8 hours incubation. Two underlying mechanisms are possible. The prompt onset of the effect of cholestane-3 beta,5 alpha,6 beta-triol may be attributable to an incorporation of the sterol into the cell membranes. On the other hand, 25-hydroxycholesterol, a potent inhibitor of cholesterol biosynthesis, may have a delayed effect on membrane function by depleting the cholesterol available for membrane synthesis.
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PMID:Effects on membrane function by cholesterol oxidation derivatives in cultured aortic smooth muscle cells. 303 30