Effect of pyrazole, cobalt and phenobarbital on mouse liver cytochrome P-450 2a-4/5 (Cyp2a-4/5) expression

Hahnemann, Birger, Salonpaa, Pirkko, Pasanen, Markku, Maenpaa, Jukka, Honkakosi, Paavo, Juvonen, Risto, Lang, Matti A., Pelkonen, Olavi and Raunio, Hannu (1992) Effect of pyrazole, cobalt and phenobarbital on mouse liver cytochrome P-450 2a-4/5 (Cyp2a-4/5) expression. Biochemical Journal, 286 1: 289-294.

Author Hahnemann, Birger
Salonpaa, Pirkko
Pasanen, Markku
Maenpaa, Jukka
Honkakosi, Paavo
Juvonen, Risto
Lang, Matti A.
Pelkonen, Olavi
Raunio, Hannu
Title Effect of pyrazole, cobalt and phenobarbital on mouse liver cytochrome P-450 2a-4/5 (Cyp2a-4/5) expression
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 1992-08
Sub-type Article (original research)
Volume 286
Issue 1
Start page 289
End page 294
Total pages 6
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Abstract Pyrazole, cobalt and phenobarbital increase the activity of coumarin 7-hydroxylase (COH) in mouse liver. To study the mechanism of this increase, we measured the expression of the cytochrome P-450 2a-4/5 (Cyp2a-4/5) complex, which mediates testosterone 15α-hydroxylase and COH activities, as a function of dose and time after the treatment of C57BL/6 (B6) and DBA/2 (D2) male mice with the inducers. COH activity and Cyp2a-4/5 steady-state mRNA levels were increased in both strains in response to the inducers. No marked effect occurred with testosterone 15α-hydroxylase or activities associated with Cypla-1 or Cyp2e-1. A 2-7-fold increase in response to the inducers was seen in the amount of P-450Coh (cytochrome P-450 isoenzyme catalysing coumarin 7-hydroxylation) protein in Western immunoblots. PCR amplification of a 1 kb region in Cyp2a-4/5-mRNA-derived cDNA, followed by cutting at the diagnostic PstI site, showed that most of the steady-state mRNA consisted of Cyp2a-5, which is also the form most affected by pyrazole. Nuclear runoff analysis revealed no increase in the transcription rate of Cyp2a-4/5 after pyrazole or cobalt treatment, whereas a 2-3-fold increase occurred after phenobarbital pretreatment in B6 mice. Together with previous reports [Aida and Negishi (1991) Biochemistry 30, 8041-8045], the current data suggest that both pyrazole and cobalt increase COH catalytic activity by affecting Cyp2a-5 by post-transcriptional mechanisms in mice.
Keyword Coumarin hydroxylase activity
Steroid 15 alpha hydrolase
Genetic regulation
II P-45015-alpha
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
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Created: Mon, 30 Nov 2009, 15:02:06 EST