JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mastyugin, V.
Right arrow Articles by Schwartzman, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mastyugin, V.
Right arrow Articles by Schwartzman, M. L.

Vol. 289, Issue 3, 1611-1619, June 1999

Hypoxia-Induced Production of 12-Hydroxyeicosanoids in the Corneal Epithelium: Involvement of a Cytochrome P-4504B1 Isoform1

Vladimir Mastyugin, Eleanor Aversa, Albino Bonazzi, Christina Vafaes, Paul Mieyal and Michal Laniado Schwartzman

Department of Pharmacology, New York Medical College, Valhalla, New York

The corneal epithelium metabolizes arachidonic acid by a cytochrome P-450 (CYP)-mediated activity to 12-hydroxy-5,8,11,14-eicosatetraenoic acid (12(R)-HETE) and 12-hydroxy-5,8,14-eicosatrienoic acid (12(R)-HETrE ). Both metabolites possess potent inflammatory properties, with 12(R)-HETrE being a powerful angiogenic factor, and they assume the role of inflammatory mediators in hypoxia- and chemical-induced injury in the cornea in vivo and in vitro. We used a model of corneal organ culture that exhibits hypoxia-induced epithelial CYP-dependent 12(R)-HETE and 12(R)-HETrE synthesis for isolating, identifying, and characterizing the CYP protein responsible for these eicosanoid syntheses. Northern analysis revealed the presence of a CYP4A-hybridizable mRNA, the levels of which were increased after hypoxia. Reverse transcription-polymerase chain reaction analysis with primers specific for the CYP4A family led to the isolation of a 671-base pair fragment with a 98.8% sequence homology to the rabbit lung CYP4B1 isoform, of which the levels in the corneal epithelium were greatly increased under hypoxic conditions. Moreover, phenobarbital, an inducer of hepatic CYP4B1 in the rabbit, also induced 12-HETE and 12-HETrE synthesis. Antibodies against CYP4B1, but not against CYP4A1, inhibited hypoxia-, clofibrate-, and phenobarbital-induced 12-HETE and 12-HETrE synthesis. These results suggest the involvement of a CYP4B1 isoform in the corneal epithelial synthesis of these eicosanoids in response to hypoxia.

0022-3565/99/2893-1611$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
Christopher. R. Chiaro, R. D. Patel, and Gary. H. Perdew
12(R)-Hydroxy-5(Z),8(Z),10(E),14(Z)-eicosatetraenoic Acid [12(R)-HETE], an Arachidonic Acid Derivative, Is an Activator of the Aryl Hydrocarbon Receptor
Mol. Pharmacol., December 1, 2008; 74(6): 1649 - 1656.
[Abstract] [Full Text] [PDF]

Home page
 Jpn J Clin OncolHome page
T. Sasaki, M. Horikawa, K. Orikasa, M. Sato, Y. Arai, Y. Mitachi, M. Mizugaki, M. Ishikawa, and M. Hiratsuka
Possible Relationship Between the Risk of Japanese Bladder Cancer Cases and the CYP4B1 Genotype
Jpn. J. Clin. Oncol., September 1, 2008; 38(9): 634 - 640.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. Patil, L. Bellner, G. Cullaro, K. H. Gotlinger, M. W. Dunn, and M. L. Schwartzman
Heme Oxygenase-1 Induction Attenuates Corneal Inflammation and Accelerates Wound Healing after Epithelial Injury
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3379 - 3386.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. Du, V. Yermalitsky, D. L. Hachey, S. G. Jagadeesh, J. R. Falck, and D. S. Keeney
A Biosynthetic Pathway Generating 12-Hydroxy-5,8,14-eicosatrienoic Acid from Arachidonic Acid Is Active in Mouse Skin Microsomes
J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 371 - 379.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Mezentsev, V. Mastyugin, F. Seta, S. Ashkar, R. Kemp, D. S. Reddy, J. R. Falck, M. W. Dunn, and M. Laniado-Schwartzman
Transfection of Cytochrome P4504B1 into the Cornea Increases Angiogenic Activity of the Limbal Vessels
J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 42 - 50.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Mezentsev, F. Seta, M. W. Dunn, N. Ono, J. R. Falck, and M. Laniado-Schwartzman
Eicosanoid Regulation of Vascular Endothelial Growth Factor Expression and Angiogenesis in Microvessel Endothelial Cells
J. Biol. Chem., May 17, 2002; 277(21): 18670 - 18676.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C.-C. Tsao, S. J. Coulter, A. Chien, G. Luo, N. P. Clayton, R. Maronpot, J. A. Goldstein, and D. C. Zeldin
Identification and Localization of Five CYP2Cs in Murine Extrahepatic Tissues and Their Metabolism of Arachidonic Acid to Regio- and Stereoselective Products
J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 39 - 47.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
E. R. Jacobs and D. C. Zeldin
The lung HETEs (and EETs) up
Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H1 - H10.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
P. A. Mieyal, A. Bonazzi, H. Jiang, M. W. Dunn, and M. L. Schwartzman
The Effect of Hypoxia on Endogenous Corneal Epithelial Eicosanoids
Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2170 - 2176.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. Bonazzi, V. Mastyugin, P. A. Mieyal, M. W. Dunn, and M. Laniado-Schwartzman
Regulation of Cyclooxygenase-2 by Hypoxia and Peroxisome Proliferators in the Corneal Epithelium
J. Biol. Chem., January 28, 2000; 275(4): 2837 - 2844.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.