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CYTOCHROME P450, SUBFAMILY IIA; CYP2A OKDB#: 1784
 Symbols: CYTOCHROME P450, SUBFAMILY IIA; CYP2A Species: human
 Synonyms: CYP2| CYP2A1| P450C2| P450C2A| CYTOCHROME P450, PHENOBARBITAL-INDUCIBLE, P450PB|  Locus: 19q13.2 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment The cytochromes P-450 are among the major constituent proteins of the liver mixed function monooxygenases. They play a central role in the metabolism of steroids, the detoxification of drugs and xenobiotics, and the activation of procarcinogens. 'Cytochrome' means literally 'colored substance in the cell.' The color is derived from the subatomic properties of the iron in this hemoprotein, and, indeed, cytochromes appear reddish when present in sufficient concentration in the test-tube. The dioxin-inducible P450 coded by chromosome 15 is called CYP1 and that the P450 coded by chromosome 19 is called CYP2A.

General function Enzyme
Comment
Cellular localization Mitochondrial
Comment
Ovarian function Steroid metabolism
Comment
Expression regulated by
Comment
Ovarian localization Granulosa
Comment Cannady EA, et al reported the Expression and Activity of Cytochromes P450 2E1, 2A, and 2B in the Mouse Ovary and The Effect of 4-Vinylcyclohexene and Its Diepoxide Metabolite. 4-Vinylcyclohexene (VCH), an occupational chemical, causes destruction of small pre-antral follicles (F1) in mice. Previous studies suggested that VCH is bioactivated via cytochromes P450 (Cyp 450) to the ovotoxic, diepoxide metabolite, VCD. Whereas hepatic Cyp 450 isoforms 2E1, 2A, and 2B can metabolize VCH, the role of ovarian metabolism is unknown. This study investigated expression of these isoforms in isolated ovarian fractions (F1, 25-100 micro m; F2, 100-250 micro m; F3, >250 micro m; interstitial cells; Int) from B6C3F1 mice dosed daily (15 d; ip) with vehicle, VCH (7.4 mmol/kg/d) or VCD (0.57 mmol/kg/d). Ovaries were removed and either isolated into specific ovarian compartments for mRNA analysis, fixed for immunohistochemistry, or prepared for enzymatic assays. mRNA and protein for all isoforms were expressed/distributed in all ovarian fractions from vehicle-treated mice. In the targeted F1 follicles, VCH or VCD dosing increased (p<0.05) mRNA encoding Cyp 2E1 (645+/-14% VCH; 582+/-16% VCD), Cyp 2A (689+8% VCH; 730+/-22% VCD), and Cyp 2B (246+/-7% VCH) above control. VCH dosing altered (p<0.05) mRNA encoding Cyp 2E1 in non-targeted F3 follicles (168+/-7%) and Cyp 2A in Int (207+/-19%) above control. Immunohistochemical analysis revealed the greatest staining intensity for all Cyp isoforms in the Int. VCH dosing altered (p<0.05) staining intensity in Int for Cyp 2E1 (19+/-2.4% below control) and Cyp 2A (39+/-5% above control). Staining intensity for Cyp 2B was increased (p<0.05) above control in granulosa cells of small pre-antral (187+/-42%) and antral (63+/-8%) follicles. Catalytic assays in ovarian homogenates revealed that Cyp 2E1 and Cyp 2B were functional. Only Cyp 2E1 activity was increased (149+/-12% above control; p<0.05) by VCH dosing. The results demonstrate that mRNA and protein for Cyp isoforms known to bioactivate VCH are expressed in the mouse ovary and are modulated by in vivo exposure to VCH and VCD. Interestingly, there is high expression of these isoforms in the Int. Thus, the ovary may contribute to ovotoxicity by promoting bioactivation of VCH to the toxic metabolite, VCD.
Follicle stages Antral
Comment
Phenotypes
Mutations 0 mutations
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created: April 23, 2003, 11:56 a.m. by: hsueh   email:
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last update: April 23, 2003, 11:56 a.m. by: system    email:



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