Nad Levels In The Rat Primary Cultured Hepatocytes Affected By Peroxisome- Proliferators
The effect of peroxisome-proliferators (PPs) on the NAD level in primary cultured rat hepatocytes was investigated and compared with that in the liver of rat administered with PPs. Various PPs, including fibrates, phthalate esters and steroid, increased NAD level in the cultured hepatocytes as in whole animal with a little exception. The NAD level decreased after once reaching the peak by the addition of most PPs. The gradual decrease of NAD observed in primary cultured hepatocytes, was partially inhibited by the addition of poly(ADP-ribose) polymerase and/or NAD glycohydrolase inhibitors. In the presence of these inhibitors, the increase of NAD by PPs still remained. The mechanism of increasing NAD level by PPs will be due to the stimulation of tryptophan (Trp)-NAD biosynthesis, with the possibility of the transcriptional regulation of genes related to TrpNAD pathway by PPs. This in vitro system, therefore, can be used to clarify detailed mechanism of the stimulation of hepatic NAD biosynthesis in rats administered PPs.
KeywordsPhthalate Ester Methylpropanoic Acid Dish Sample Floating Collagen Membrane Peroxisomal Marker Enzyme
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- 5.M.Shin, S. Nakakita, C. Hashimoto, K. Sano, C. Umezawa, NAD’ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes-Effect of clofibrate-feeding, Internat. J. Vit. Nutr. Res. 68 104-108 (1998).Google Scholar
- 11.P. A. Ram, D. J. Waxman, Dehydroepiandrosterone 3(3-sulphate is an endogenous activator of the peroxisome-proliferation pathway: induction of cytochrome P-450 4A and acyl-CoA oxidase mRNAs in primary rat hepatocyte culture and inhibitory effects of Ca2+-channel blockers, Biochem. J. 301,753-758 (1994).PubMedGoogle Scholar