Abstract
The loss of cytochrome P-450 in cultured rat hepatocytes can be prevented by substituted pyridines, especially isonicotinamide, 3-hydroxypyridine and metyrapone. The effect of these compounds is independent of protein synthesis, suggesting that they maintain pre-existing cytochrome P-450. The efficiency of pyridines at maintaining cytochrome P-450 in hepatocyte culture is highly correlated with their ability to bind to this cytochrome, suggesting that ligand formation with cytochrome P-450 prevents its accelerated turnover in liver cell culture.
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- Guzelian P. S., Barwick J. L. Inhibition by cycloheximide of degradation of cytochrome P-450 in primary cultures of adult rat liver parenchymal cells and in vivo. Biochem J. 1979 Jun 15;180(3):621–630. doi: 10.1042/bj1800621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guzelian P. S., Bissell D. M., Meyer U. A. Drug metabolism in adult rat hepatocytes in primary monolayer culture. Gastroenterology. 1977 Jun;72(6):1232–1239. [PubMed] [Google Scholar]
- Hildebrandt A. G., Leibman K. C., Estabrook R. W. Metyrapone interaction with hepatic microsomal cytochrome P-450 from rats treated with phenobarbital. Biochem Biophys Res Commun. 1969 Oct 22;37(3):477–485. doi: 10.1016/0006-291x(69)90940-1. [DOI] [PubMed] [Google Scholar]
- Jefcoate C. R., Gaylor J. L., Calabrese R. L. Ligand interactions with cytochrome P-450. I. Binding of primary amines. Biochemistry. 1969 Aug;8(8):3455–3463. doi: 10.1021/bi00836a049. [DOI] [PubMed] [Google Scholar]
- McLean A. E., Day P. A. The use of new methods to measure: the effect of diet and inducers of microsomal enzyme synthesis on cytochrome P-450 in liver homogenates, and on metabolism of dimethyl nitrosamine. Biochem Pharmacol. 1974 Apr 1;23(7):1173–1180. doi: 10.1016/0006-2952(74)90291-3. [DOI] [PubMed] [Google Scholar]
- Paine A. J., Hockin L. J., Legg R. F. Relationship between the ability of nicotinamide to maintain nicotinamide-adenine dinucleotide in rat liver cell culture and its effect on cytochrome P-450. Biochem J. 1979 Nov 15;184(2):461–463. doi: 10.1042/bj1840461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paine A. J., Legg R. F. Apparent lack of correlation between the loss of cytochrome P-450 in hepatic parenchymal cell culture and the stimulation of haem oxygenase activity. Biochem Biophys Res Commun. 1978 Mar 30;81(2):672–679. doi: 10.1016/0006-291x(78)91589-9. [DOI] [PubMed] [Google Scholar]
- Schenkman J. B., Remmer H., Estabrook R. W. Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol Pharmacol. 1967 Mar;3(2):113–123. [PubMed] [Google Scholar]
- Temple D. J. Binding of nitrogen containing compounds to microsomal cytochromes. Xenobiotica. 1971 Jul-Oct;1(4):507–520. doi: 10.3109/00498257109041519. [DOI] [PubMed] [Google Scholar]