Inhibition of Cytochrome P450 Enzymes by Nitric Oxide
Inflammatory Stimulation of the liver causes significant alterations in liver cell metabolism. Recent experimental studies indicate that induction of nitric oxide (NO) biosynthesis may play a major role in the regulation of inflammatory processes and subsequent metabolic changes (23). Under cell culture conditions bacterial toxins and proinflammatory cytokines, such as TNFα, IL-1 and IFNγ, were identified as inducers of NO biosynthesis in parenchymal as well as non-parenchymal liver cells (6). Hepatic NO biosynthesis was also demonstrated in several animal models for local or systemic inflammation including injection of Corynebacterium parvum or lipopolysaccharides (4, 10). Finally, human hepatocytes were shown to express inducible nitric oxide synthase (iNOS) activity, which set the basis for cloning and heterologous expression of the human iNOS gene (24, 11). These findings support the idea that NO biosynthesis of the liver is a clinically relevant phenomenon in diseases characterized by local or systemic inflammatory reactions.
KeywordsNitric Oxide Nitric Oxide Electron Paramagnetic Resonance Electron Paramagnetic Resonance Signal Human Hepatocyte
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- 10.Geller, D. A., P. D. Freeswick, D. Nguyen, A. K. Nüssler, M. Di Silvio, R. A. Shapiro, S. C. Wang, R. L. Simmons, and T. R. Billiar. Differential induction of nitric oxide synthase in hepatocytes during endotoxemia and the acute-phase response. Arch Surg. 129: 165–171, 1994.PubMedCrossRefGoogle Scholar
- 11.Geller, D. A., C. J. Lowenstein, R. A. Shapiro, A. K. Nüssler, M. Di Silvio, S. C. Wang, D. K. Nakayama, R. L. Simmons, S. H. Snyder, and T. R. Billiar. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci USA. 90: 3491–3495, 1993.PubMedCrossRefGoogle Scholar
- 19.Lancaster jr, J. R. Diffusion and reactions of nitric oxide in isolated hepatocytes. First International Conference: Biochemistry and Molecular Biology of Nitric Oxide. Los Angeles, CA: July 16–21, 1994, 1994.Google Scholar
- 21.Molina y Vedia, L., B. McDonald, B. Reep, B. Brune, M. Di Silvio, T. R. Billiar, and E. G. Lapetina. Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. J Biol Chem. 261: 24929–24932, 1992.Google Scholar
- 25.O’Keefe, D., R. Ebel, and J. Peterson. Studies of the oxygen binding site of cytochrome p-450. J Biol Chem. 253: 3509–3516, 1978.Google Scholar