Cytochrome P450 gender-related differences in response to hyperoxia in young CBA mice.

Abstract

Cytochrome P450 monooxygenases (CYPs) represent large class of heme-containing enzymes that catalyze the metabolism of various endogenous and exogenous substrates. Although they are found in many tissues, the function of the particular subset of their isoforms does not appear to be the same. Many CYP genes exhibit sexually dimorphic expression, while others are sex-independent. Moreover, as a source of reactive oxygen species (ROS), P450 system is believed to play the important role in various pathological conditions and diseases. The aim of this study was to observe the effect of hyperoxia on oxidant/antioxidant status in the liver of young male and female mice and to determine whether the observed effects are associated with the expression of Heme oxygenase-1 (HO-1) and CYP genes associated with stress (Cyp1a1, Cyp1a2, Cyp2a5, and Cyp2e1) or stress and gender-related responses (Cyp2b9). In this study, we demonstrated gender-related effect of hyperoxia on oxidant/antioxidant status and on expression of certain P450 enzymes. Our results suggest that females are less susceptible to hyperoxia induced oxidative stress by two major mechanisms: upregulated expression of HO-1 genes and different expression of certain P450 enzymes. Therefore, our study could provide additional data of gender-dependent responses in susceptibility to oxidative stress, chemical toxicity and drug efficiency in treatment of diseases.

• Authors: Zeljka Mačak-Šafranko, Sandra Sobočanec, Ana Sarić, Tihomir Balog, Višnja Sverko, Borka Kušić, Tanja Marotti
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 63 Issue 4 Pg. 345-50 (May 2011) ISSN: 1618-1433 [Electronic] Germany
• PMID: 20227864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier GmbH. All rights reserved.

Chemical References

• Cytochrome P-450 Enzyme System
• Heme Oxygenase-1

Topics

• Aging
• Animals
• Cytochrome P-450 Enzyme System (biosynthesis, genetics)
• Female
• Gene Expression
• Heme Oxygenase-1 (biosynthesis, genetics)
• Hyperoxia (genetics, metabolism)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred CBA
• Oxidative Stress (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sex Characteristics
• Up-Regulation