We previously cloned and demonstrated four distinct types of regulation of P450llE1. During the past year, we demonstrated two additional mechanisms of P450llE1 regulation: translational activation of P45OllE1 by isoniazid and pyrazine; and pretranslational suppression of hepatic P45OllE1 during pregnancy. Specific translational induction of P45OllE1 by isoniazid and pyrazine was demonstrated. However, pyridazine and pyrimidine, two stereoisomers of pyrazine, did not activate P45OllE1, indicating a more inflexible structural requirement for P450llE1 mRNA translation into its protein. In contrast, pyrrole with five-membered ring structure reduced P45OllE1 activity resulting from rapid reversal (within 1 day) upon parturition were also demonstrated. Exogenously administered steroids (progesterone, estrogen, and thyroxine) and peptide growth factors (placental lactogen, prolactin, and growth hormone) did not cause significant changes in P45OllE1 level. The changes in P45OllE1 was only observed in liver but not in extrahepatic tissues, suggesting a potential role of hepatocyte growth factor in P45OllE1 regulation. In collaboration with Dr. Ravindranath, the presence of P45OllE1 in brain and its induction after chronic ethanol drinking were demonstrated. We also showed that P45OllE1 can be phosphorylated by protein kinase C, cAMP dependent protein kinase or calmodulin-dependent protein kinase.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Intramural Research (Z01)
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National Institute on Alcohol Abuse and Alcoholism
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Moon, Kwan-Hoon; Upreti, Vijay V; Yu, Li-Rong et al. (2008) Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated mitochondrial dysfunction in rat liver. Proteomics 8:3906-18
Song, Byoung-Joon; Moon, Kwan-Hoon; Olsson, Nils U et al. (2008) Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids. J Hepatol 49:262-73
Moon, Kwan-Hoon; Abdelmegeed, Mohamed A; Song, Byoung-Joon (2007) Inactivation of cytosolic aldehyde dehydrogenase via S-nitrosylation in ethanol-exposed rat liver. FEBS Lett 581:3967-72
Moon, Kwan-Hoon; Hood, Brian L; Kim, Bong-Jo et al. (2006) Inactivation of oxidized and S-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats. Hepatology 44:1218-30
Kim, Bong-Jo; Hood, Brian L; Aragon, Richard A et al. (2006) Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells. Proteomics 6:1250-60
Lee, Yun-Sik; Wan, Jie; Kim, Bong-Jo et al. (2006) Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen. J Pharmacol Exp Ther 317:202-8
Wan, Jie; Ernstgard, Lena; Song, Byoung J et al. (2006) Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats. J Pharm Pharmacol 58:51-61
Moon, Kwan-Hoon; Kim, Bong-Jo; Song, Byoung J (2005) Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide-mediated S-nitrosylation. FEBS Lett 579:6115-20
Suh, Soo-Kyung; Hood, Brian L; Kim, Bong-Jo et al. (2004) Identification of oxidized mitochondrial proteins in alcohol-exposed human hepatoma cells and mouse liver. Proteomics 4:3401-12
Jeong, Won-Ii; Do, Sun-Hee; Yun, Hae-Sun et al. (2004) Hypoxia potentiates transforming growth factor-beta expression of hepatocyte during the cirrhotic condition in rat liver. Liver Int 24:658-68

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