Chinese hamster ovary cell culture

The effect of 26-hydroxycholesteroI and other intermediates in bile acid synthesis on HMG-CoA reductase activity was studied in Chinese hamster ovary (CHO) cell culture. Incubation of CHO cells for 5 hr in 0.25 PM 26-hydroxycholesterol caused a 40% inhibition of HMG-CoA reductase activity. All other intermediates tested including 3B-hydroxy-5cholenoic acid and cholest-5-ene-3B,7a,26-triol, oxidation products of 26-hydroxycholesterol, had little or no inhibitory effect.l It is proposed that 26-hydroxycholesterol has a selective biological role in the regulation of cholesterol synthesis.-Esterman, A. L., H. Baum, N. B. Javitt, and G. J. Darlington. 26-Hydroxycholesterol: regulation of hydroxymethylglutaryl-CoA reductase activity in Chinese hamster ovary cell cu1ture.J. Lipid Res. 1983. 2 4 1304-1309. Supplementary key words 26-hydroxycholesterol 7a-hydroxycholesterol 3fl-hydroxy-5-cholenoic acid bile acid intermediates HMGCoA reductase Recently, we reported that 26-hydroxycholestero1 (cholest-5-ene-SP, 26-diol) normally occurs in adult human serum (1) and is deficient in amount in individuals with the genetically determined disease, cerebrotendinous xanthomatosis (CTX) (2), who lack the hepatic mitochondrial enzyme C27-steroid 26-hydroxylase (3). In view of the potent biological effects of 25-hydroxycholesterol (4), we undertook a study of the effect of 26-hydroxycholestero1 and its derivatives on the activity of hydroxymethylglutaryl CoA (HMG-CoA) reductase (EC 1.1.1.34) in Chinese hamster ovary (CHO) cells, a well-established mode9 for the study of sterol synthesis (5-7). EXPERIMENTAL PROCEDURES