title: Regulation of 3-hydroxy-3-methylglutaryl CoA reductase by analogs of cholesterol and bile acids in cultured intestinal mucosa.
abstract: Sodium fusidate and its glycine conjugate, which have the same detergent properties as bile acids, significantly (p less than 0.05) stimulate HMG-CoA reductase of cultured intestine below the critical micellar concentration (CMC) without affecting brush border enzymes. Above CMC, both amphiphiles are cytotoxic. At concentrations between 1 and 5 mM, sodium fusidate decreased cholesterol contents of cultured mucosa (P less than 0.05), the increase in synthesis only partially compensating for the sterol loss. Oxygenated sterols, 7-keto- and 25-hydroxycholesterol, also depleted mucosal cholesterol at 0.5 mM, exerting their effect differently by inhibiting HMG-CoA reductase (p less than 0.01). In contrast to their marked effect on total mucosal cholesterol contents, brush border cholesterol was unaffected by both cholesterol and bile acid analogs.
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005672:Fusidic Acid / Q000494:pharmacology*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007413:Intestinal Mucosa / Q000378:metabolism*; D007653:Ketocholesterols / Q000494:pharmacology*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits
chemical_list: D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007653:Ketocholesterols; D005672:Fusidic Acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases