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Am J Physiol Lung Cell Mol Physiol (July 25, 2003). doi:10.1152/ajplung.00039.2003
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Submitted on February 6, 2003
Accepted on July 18, 2003

Pulmonary cytochrome P450 2J4 (CYP2J4) is reduced in a rat model of acute Pseudomonas pneumonia

Asma Yaghi1, J. Alyce Bradbury2, Darryl C. Zeldin2, Sanjay Mehta3, John R. Bend4, and David G. McCormack3*

1 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada; Respirology, London Health Sciences Centre, Victoria Campus, AC Burton Vascular Biology Laboratory, Lawson Health Research Institute, London, ON, Canada
2 NIH, National Institute of Environmental Health Sciences, Research Triangle park, N.C. 27709, USA
3 Respirology, London Health Sciences Centre, Victoria Campus, AC Burton Vascular Biology Laboratory, Lawson Health Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
4 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada

* To whom correspondence should be addressed. E-mail: david.mccormack{at}lhsc.on.ca.

We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy into the lungs of rats. Forty-four hours later, lungs were frozen and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4 and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared to control lung microsomes. The CYP2B bands (51-52kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunologic characteristics similar to CYP2J4 and this CYP is reduced following pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats.




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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Yaghi, J. R. Bend, C. D. Webb, D. C. Zeldin, S. Weicker, S. Mehta, and D. G. McCormack
Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia
Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1260 - L1267.
[Abstract] [Full Text] [PDF]


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