Details

Autor(en) / Beteiligte

• Levitchi, Mihaela
• Fradette, Caroline
• Bleau, Anne-Marie
• Michaud, Dorothée
• Kourylko, Oksana
• Arcand, Mathieu
• du Souich, Patrick

Titel

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

Ist Teil von

• Biochemical pharmacology, 2004-08, Vol.68 (3), p.573-582

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 4 h 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 4 h 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 demonstrated that the decrease in total cytochrome P450 content and in CYP1A1/1A2 and 3A6 activity by sera and interleukin-6 involves the activation of protein tyrosine kinases, p42/44 mitogen-activated protein kinase and protein kinase C. Indirect evidence supported that nitric oxide is implicated in the decrease in activity of these enzymes.