Signal transduction pathways implicated in the decrease in CYP1A1, 1A2 and 3A6 activity produced by serum from rabbits and humans with an inflammatory reaction

Biochemical Pharmacology
M C LevitchiPatrick du Souich

Abstract

Incubation of serum from rabbits with a turpentine-induced inflammatory reaction and from humans with an upper respiratory viral infection with hepatocytes from rabbits with a turpentine-induced inflammatory reaction for 4h reduces total cytochrome P450 content and activity of cytochrome P450 isoforms CYP1A1/1A2 and 3A6 without affecting the expression of these proteins. To document the signal transduction pathways implicated in the decrease in CYP1A1/1A2 and 3A6 activity, hepatocytes from rabbits with a turpentine-induced inflammatory reaction were incubated with serum from rabbits with a turpentine-induced inflammatory reaction, serum from individuals with a viral infection and interleukin-6 for 4h in presence of inhibitors of protein kinases. The sera-induced decrease in CYP1A1/1A2 and 3A6 activity was partially prevented by the inhibition of Janus-associated protein tyrosine kinase, double-stranded RNA-dependent protein kinase, protein kinase C, and p42/44 mitogen-activated protein kinase. The serum from rabbits with a turpentine-induced inflammatory reaction increased the phosphorylation of Erk1/2, effect prevented by PD98059 but not by bis-indolylmaleimide, a specific inhibitor of protein kinase C. The results demonstrate...Continue Reading

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Citations

Jan 13, 2006·Annual Review of Pharmacology and Toxicology·Alison E AitkenEdward T Morgan
Jul 11, 2012·Fibrogenesis & Tissue Repair·Chandrashekhar R Gandhi
Sep 1, 2008·Expert Review of Clinical Pharmacology·Guillaume DumaisPatrick du Souich
Oct 6, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Oksana KourylkoPatrick du Souich
Oct 11, 2005·The Journal of Pharmacology and Experimental Therapeutics·Wolfgang E ThaslerThomas S Weiss
Apr 25, 2018·Mediators of Inflammation·Wen-Yao ZhangMing-Qing Gao

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