Journal article
Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain
The Journal of biological chemistry, v 276(27), pp 25467-25479
06 Jul 2001
PMID: 11328810
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A cDNA encoding a new cytochrome P450 was isolated from a mouse brain library. Sequence analysis reveals that this 1,958-base pair cDNA encodes a 57-58-kDa 502-amino acid polypeptide that is 70-91% identical to CYP2J subfamily P450s and is designated CYP2J9. Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450 oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system. Microsomes of CYP2J9/CYPOR-transfected cells metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid (HETE) thus CYP2J9 is enzymologically distinct from other P450s. Northern analysis reveals that CYP2J9 transcripts are present at high levels in mouse brain. Mouse brain microsomes biosynthesize 19-HETE. RNA polymerase chain reaction analysis demonstrates that CYP2J9 mRNAs are widely distributed in brain and most abundant in the cerebellum. Immunoblotting using an antibody raised against human CYP2J2 that cross-reacts with CYP2J9 detects a 56-kDa protein band that is expressed in cerebellum and other brain segments and is regulated during postnatal development. In situ hybridization of mouse brain sections with a CYP2J9-specific riboprobe and immunohistochemical staining with the anti-human CYP2J2 IgG reveals abundant CYP2J9 mRNA and protein in cerebellar Purkinje cells. Importantly, 19-HETE inhibits the activity of recombinant P/Q-type Ca(2+) channels that are known to be expressed preferentially in cerebellar Purkinje cells and are involved in triggering neurotransmitter release. Based on these data, we conclude that CYP2J9 is a developmentally regulated P450 that is abundant in brain, localized to cerebellar Purkinje cells, and active in the biosynthesis of 19-HETE, an eicosanoid that inhibits activity of P/Q-type Ca(2+) channels. We postulate that CYP2J9 arachidonic acid products play important functional roles in the brain.
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Details
- Title
- Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain
- Creators
- W Qu - National Institute of Environmental Health SciencesJ A Bradbury - National Institute of Environmental Health SciencesC C Tsao - National Institute of Environmental Health SciencesR Maronpot - National Institute of Environmental Health SciencesG J Harry - National Institute of Environmental Health SciencesC E Parker - National Institutes of HealthL S Davis - National Institute of Environmental Health SciencesM D Breyer - Vanderbilt UniversityM P Waalkes - National Institute of Environmental Health SciencesJ R Falck - The University of Texas Southwestern Medical CenterJ Chen - University of North Carolina at Chapel HillR L Rosenberg - University of North Carolina at Chapel HillD C Zeldin - National Institutes of Health
- Publication Details
- The Journal of biological chemistry, v 276(27), pp 25467-25479
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC; BETHESDA
- Number of pages
- 13
- Grant note
- HL49449 / NHLBI NIH HHS GM-31278 / NIGMS NIH HHS P01-DK38226 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000169800700137
- Scopus ID
- 2-s2.0-0035816583
- Other Identifier
- 991021902525304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology