Differential sensitivity of rat hepatocyte CYP isoforms to self‐generated nitric oxide
- 12 January 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 488 (1-2) , 59-63
- https://doi.org/10.1016/s0014-5793(00)02388-7
Abstract
Early loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study investigates the influence of endogenously generated NO (or NO‐derived species) on the relative expression of cytochrome P450 (CYP) isoforms in rat hepatocytes. Our results support the view that loss of P450 holoenzyme in culture is the ultimate consequence of a NO driven process, activated during the common hepatocyte isolation procedure, that leads to an accelerated and selective degradation of specific CYP apoproteins. Under conditions in which NO and peroxynitrite formation is operative, changes in the level of specific CYP isoforms result in a significant alteration of the CYP apoprotein profile that after 24 h of culture is quite different from that found in the liver of uninduced rats. This process is reverted by the early and efficient inhibition of NO synthesis, which allows for (1) maintenance of total P450 holoenzyme content, (2) preservation of the initial constitutive CYP pattern in culture and (3) the early expression of the normal inducibility in response to model inducers.Keywords
This publication has 15 references indexed in Scilit:
- Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short‐term cultured hepatocytesFEBS Letters, 2000
- Peroxynitrite Reaction with Heme ProteinsNitric Oxide, 1999
- Endogenous nitric oxide is responsible for the early loss of P450 in cultured rat hepatocytesFEBS Letters, 1998
- Peroxynitrite-Mediated Nitration of Tyrosine and Inactivation of the Catalytic Activity of Cytochrome P450 2B1Chemical Research in Toxicology, 1998
- Loss and Degradation of Enzyme-bound Heme Induced by Cellular Nitric Oxide SynthesisJournal of Biological Chemistry, 1995
- Inhibition of cytochromes P4501A by nitric oxide.Proceedings of the National Academy of Sciences, 1994
- Inhibition of Cytochromes P450 by Nitric Oxide and a Nitric Oxide-Releasing AgentArchives of Biochemistry and Biophysics, 1993
- The maintenance of cytochrome P-450 in rat hepatocyte culture: Some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P-450 systemChemico-Biological Interactions, 1990
- Active glycolysis and glycogenolysis in early stages of primary cultured hepatocytes. Role of AMP and fructose 2.6-bisphosphateIn Vitro Cellular & Developmental Biology, 1988
- [22] The measurement of difference spectra: Application to the cytochromes of microsomesPublished by Elsevier ,1978