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Isolation of Hybridomas Producing Monoclonal Antibodies (MAbs) Inhibitory to Human CYP2J2

Posted Oct 31 2003 4:00pm

Description of Invention:
Cytochromes P450 catalyze the NADPH-dependent oxidation of arachidonic acid to various eicosanoids found in several species. The eicosanoids are biosynthesized in numerous tissues including pancreas, intestine, kidney, heart, and lung where they are involved in many different biological activities.

The NIH announces three specific monoclonal antibodies that strongly inhibit and/or immunoblot the human cytochrome P450 2J2 (CYP2J2). MAb 6-5-20-8 selectively inhibits CYP2J2-mediated arachidonic acid metabolism by more that 80% and also immunoblots the enzyme. MAb 6-2-16-1 also selectively inhibits arachidonic acid metabolism by more that 80%, but does not immunoblot the enzyme. MAb 5-3-2-2 is not inhibitory, but selectively immunoblots the enzyme. These antibodies can be used to identify and quantify inter-individual variation in physiological functions and to study pharmacological drug metabolism in various tissues.

Inventors:
Darryl C Zeldin (NIEHS)
Harry V Gelboin (NCI)


Patent Status:
HHS, Reference No. E-337-2003/0


Relevant Publication:
  1. Wu, S., Moomaw, C., Tomer, K.B., Falck, J.R., and Zeldin, D.C. Molecular Cloning and Expression of CYP2J2, a Human Cytochrome P450 Arachidonic Acid Epoxygenase Highly Expressed in Heart. Journal of Biological Chemistry 271: 3460-3468, 1996.
  2. Node, K., Huo, Y., Ruan, L.-L., Yang, B., Spiecker, M., Ley, K., Zeldin, D.C., and Liao, J.K. Anti-inflammatory Actions of Epoxygenase-Derived Eicosanoids. Science 285: 1276-1279, 1999.
  3. Node, K., Ruan, X.-L., Dai, J., Yang, S.-X., Graham, L., Zeldin, D.C., and Liao, J.K. Activation of Gas Mediates Induction of Tissue-type Plasminogen Activator Gene Transcription by Epoxyeicosatrienoic Acids. Journal of Biological Chemistry 276: 15983-15989, 2001.
  4. Zeldin, D.C. Epoxygenase Pathways of Arachidonic Acid Metabolism. Journal of Biological Chemistry 276: 36059-36062, 2001.
  5. Yang, B., Graham, L., Kikalov, S., Mason, R.P., Falck, J.R., Liao, J.K., and Zeldin, D.C. Overexpression of Cytochrome P450 CYP2J2 Protects Against Hypoxia-Reoxygenation Injury in Cultured Bovine Aortic Endothelial Cells. Molecular Pharmacology 60: 310-320, 2001.
  6. King, L.M., Ma, J., Srettabunjong, S., Graves, J., Bradbury, J.A., Li, L., Spiecker, M., Liao, J.K., Mohrenweiser, H., and Zeldin, D.C. Cloning of the CYP2J2 Gene and Identification of Functional Polymorphisms. Molecular Pharmacology 61: 840-852, 2002.
  7. Sun, J., Sui, X., Bradbury, J.A., Zeldin, D.C., Conte, M.S., and Liao, J.K. Inhibition of Vascular Smooth Muscle Cell Migration by Cytochrome P450 Epoxygenase-Derived Eicosanoids. Circulation Research 90: 1020-1027, 2002.



Portfolios:
Internal Medicine
Internal Medicine - Research Materials



For Additional Information Please Contact:
Fatima Sayyid MHPM
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 21,
Rockville, MD 20852
United States
Email: Fatima.Sayyid@nih.hhs.gov
Phone: 301-435-4521
Fax: 301-402-0220


Ref No: 777

Updated: 11/2003

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