title: Effects on membrane function by cholesterol oxidation derivatives in cultured aortic smooth muscle cells.
abstract: 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.
mesh_terms: D015720:5'-Nucleotidase; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D002478:Cells, Cultured; D002777:Cholestanols / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009708:Nucleotidases / Q000037:antagonists & inhibitors; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D002777:Cholestanols; D006888:Hydroxycholesterols; C000474:cholestane-3,5,6-triol; C007997:25-hydroxycholesterol; D002784:Cholesterol; D003847:Deoxyglucose; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase