Gene Isolated hepatocytes

Majano, Pi., Garcfa-Monzon, C., Garcfa-Ttevijano, E.R., Corrales, F.J., Camara, J., Ortiz, P, Mato, JM., AvUa, M.A., and Moreno-Otero, R. (2001). S-adenosylmethionine modulates inducible nitric oxide synthase gene expression in rat liver and isolated hepatocytes. J. Hepatol. 35, 692-699. 

A human gene for hepatic inducible NOS was isolated in 1993 by Geller and coworkers76. Hepatocytes were isolated from an operative wedge resection, which were over 98% pure. The cells were stimulated with cytokines TNF-a, IL-1 and IFN-y. The purified cDNA, in addition to FMN, FAD and NADPH factors, also contained a calmodulin site. This site retained some activity in the presence of calcium inhibitors. There are also phosphorylation sites at 232, 576 and 890 residues. 

Pitarque M, Rodriguez-Antona C, Oscarson M, Ingelman-Sundberg M (2005) Transcriptional regulation of the human CYP2A6 gene, J Pharmacol Exp Ther 313 814-822 Poole A, Urwin C (1976) The metabolism of (14C)nicotine by isolated rhesus monkey hepatocytes in vitro, Biochem Pharmacol 25 281-283... 

The first NOS to be isolated and the gene sequenced was the rat cerebellar enzyme, by Bredt and Snyder in 1991. Since then, the sequences for aU three isoforms have been determined human brain, human and bovine endothelial, mouse macrophage, and recently the cytokine-inducible NOS from human hepatocytes. There is substantial sequence identity between the same isoforms in different species rat and human brain (93% ) and bovine and human endothelial (94% ). The identity between different isoforms (even in the same species) is substantially less, between 50 and 60%. An exception is the homology between the human hepatocyte and the mouse macrophage euzymes,... 

Harris AJ, Shaddock JG, Delongchamp R, Dragan Y, Casciano DA (2004) Comparison of Basal gene expression in cultured primary rat hepatocytes and freshly isolated rat hepatocytes. Toxicol Mech Methods 14 257-270... 

Slc22/Organic Ion Transporter Family. Few studies have reported the induction of Slc22a genes by PXR activators. By using rat hepatoma RL-34 cells, cultured primary rat hepatocytes and animals, it was shown that PCN induced the expression of rat hepatic Octl (Slc22al) mRNA. Induction of Octl transporter activity was further demonstrated ex vivo by increased uptake of the prototypical substrate MPP+ into hepatocytes, which were isolated from PCN-treated rats, compared to cells, which were isolated from control animals and in vivo by an increase in biliary excretion of TEA in PCN-treated rats [130]. 

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