Regulation of 3-hydroxy-3-methylglutaryl CoA reductase by analogs of cholesterol and bile acids in cultured intestinal mucosa.
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.
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
D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007653:Ketocholesterols; D005672:Fusidic Acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases