Biomedical Research Education & Training
Faculty Member

Capdevila, Jorge H., Ph.D.
Professor of Medicine, Emeritus

Lab Url: N/A

Phone Number: 615-322-4968

Email Address: Jorge.Capdevila@vanderbilt.edu

Capdevila, Jorge's picture
Academic history
B.S., University of Chile, Santiago, Chile
, University of Chile, Santiago, Chile
Ph.D., University of Georgia, Athens, GA
Post-doc., Karolinska Institutet, Stockholm, Sweden

Office Address   Mailing Address

S-3223 Medical Center North Vanderbilt University
Nashville, TN 37232-0146

S-3223 MCN 2372


Research Specialty
Biological oxidations/bioactive lipids/hypertension

Research Description
Functional role of the microsomal mono-oxygenase system in the metabolic transformation of fatty acids such as arachidonic acid to biologically active lipids. Role of these mediators in the control of membrane ion transport, vascular reactivity and renal function.

Several cytochrome P450 enzymes have been purified or, alternatively, their cDNAs cloned and expressed. Purified or recombinant proteins are been used for studies of their catalytic and regulatory properties. Functional significance is being studied by analysis of the effects on individual metabolites on the cellular levels of ions such as Ca++ and Na+. Cloned cDNA are being transfected into isolated cells for further biochemical and physiological characterization of this metabolic pathway. Targeted gene disruption is used for the analysis of gene specific physiological and/or pathophysiological phenotypes, and of the role of these enyzmes in diseases such as hypertesion and diabetes. .

Publications
Pozzi, A, Popescu, V, Yang, S, Mei, S, Shi, M, Puolitaival, SM, Caprioli, RM, Capdevila, JH. The anti-tumorigenic properties of peroxisomal proliferator-activated receptor alpha are arachidonic acid epoxygenase-mediated. J Biol Chem, 285(17), 12840-50, 2010 PMCID:2857132

Yang, S, Wei, S, Pozzi, A, Capdevila, JH. The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis. Arch Biochem Biophys, 489(1-2), 82-91, 2009 PMCID:2857132

Chen, JK, Chen, J, Imig, JD, Wei, S, Hachey, DL, Guthi, JS, Falck, JR, Capdevila, JH, Harris, RC. Identification of novel endogenous cytochrome p450 arachidonate metabolites with high affinity for cannabinoid receptors. J Biol Chem, 283(36), 24514-24, 2008 PMCID:2528993

Gainer, JV, Lipkowitz, MS, Yu, C, Waterman, MR, Dawson, EP, Capdevila, JH, Brown, NJ, , . Association of a CYP4A11 variant and blood pressure in black men. J Am Soc Nephrol, 19(8), 1606-12, 2008 PMCID:2488260

Pozzi, A, Capdevila, JH. PPARalpha Ligands as Antitumorigenic and Antiangiogenic Agents. PPAR Res, 2008, 906542, 2008 PMCID:2517125

Capdevila, JH. Regulation of ion transport and blood pressure by cytochrome p450 monooxygenases. Curr Opin Nephrol Hypertens, 16(5), 465-70, 2007 PMCID:2488260

Capdevila, JH, Falck, JR, Imig, JD. Roles of the cytochrome P450 arachidonic acid monooxygenases in the control of systemic blood pressure and experimental hypertension. Kidney Int, 72(6), 683-9, 2007 PMCID:2488260

Chen, J, Chen, JK, Falck, JR, Anjaiah, S, Capdevila, JH, Harris, RC. Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite. Mol Cell Biol, 27(8), 3023-34, 2007 PMCID:1899952

Pozzi, A, Ibanez, MR, Gatica, AE, Yang, S, Wei, S, Mei, S, Falck, JR, Capdevila, JH. Peroxisomal proliferator activated receptor(alpha)-dependent inhibition of endothelial cell proliferation and tumorigenesis. J Biol Chem, 2007

Nakagawa, K, Holla, VR, Wei, Y, Wang, WH, Gatica, A, Wei, S, Mei, S, Miller, CM, Cha, DR, Price, E, Zent, R, Pozzi, A, Breyer, MD, Guan, Y, Falck, JR, Waterman, MR, Capdevila, JH. Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel. J Clin Invest, 116(6), 1696-702, 2006 PMCID:1459070

Wei, S, Brittin, JJ, Falck, JR, Anjaiah, S, Nithipatikom, K, Cui, L, Campbell, WB, Capdevila, JH. Chiral resolution of the epoxyeicosatrienoic acids, arachidonic acid epoxygenase metabolites. Anal Biochem, 2006

Du, L, Yermalitsky, V, Ladd, PA, Capdevila, JH, Mernaugh, R, Keeney, DS. Evidence that cytochrome P450 CYP2B19 is the major source of epoxyeicosatrienoic acids in mouse skin. Arch Biochem Biophys, 435(1), 125-33, 2005

Gainer, JV, Bellamine, A, Dawson, EP, Womble, KE, Grant, SW, Wang, Y, Cupples, LA, Guo, CY, Demissie, S, O''Donnell, CJ, Brown, NJ, Waterman, MR, Capdevila, JH. Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation, 111(1), 63-9, 2005

Pozzi, A, Macias-Perez, I, Abair, T, Wei, S, Su, Y, Zent, R, Falck, JR, Capdevila, JH. Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids. J Biol Chem, 280(29), 27138-46, 2005

Pozzi, A, Yan, X, Macias-Perez, I, Wei, S, Hata, AN, Breyer, RM, Morrow, JD, Capdevila, JH. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J Biol Chem, 279(28), 29797-804, 2004

Bellamine, Aouatef, Wang, Yarong, Waterman, Michael R, Gainer, James V, Dawson, Elliot P, Brown, Nancy J, Capdevila, Jorge H. Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys, 409(1), 221-7, 2003

Capdevila, Jorge H, Nakagawa, Kiyoshi, Holla, Vijaykumar. The CYP P450 arachidonate monooxygenases: enzymatic relays for the control of kidney function and blood pressure. Adv Exp Med Biol, 525, 39-46, 2003

Ladd, Patricia A, Du, Liping, Capdevila, Jorge H, Mernaugh, Raymond, Keeney, Diane S. Epoxyeicosatrienoic acids activate transglutaminases in situ and induce cornification of epidermal keratinocytes. J Biol Chem, 278(37), 35184-92, 2003

Nakagawa, Kiyoshi, Marji, Jackleen S, Schwartzman, Michal L, Waterman, Michael R, Capdevila, Jorge H. Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension. Am J Physiol Regul Integr Comp Physiol, 284(4), R1055-62, 2003

Falck, J.R., Katipally, K.R., Capdevila, J.H., and Ulug, E.T. (2001) Concise synthesis of L-a-phosphatidyl-D-myo-inositol 3-phosphate (3-PIP), 5-phosphate (5-PIP), and 3,5-bisphosphate (3,5-PIP2). (Submitted).

Falck, J.R., Kumar, S.P., Reddy, K., and Zou, G. (2001) Stereospecific synthesis of EET metabolites via Suzuki-Miyaura coupling. Tet. Lett. (submitted).

Reddy, K.K., Ye, J., Falck, J.R., and Capdevila, J.H. (2001) Intracellular second messengers: Synthesis of L--phosphatidyl-D-my-inositol 3,4-bisphosphate and analogs. Biorg. Med. Chem. Lett. (In press).

Capdevila, J H, Harris, R C, Falck, J R. Microsomal cytochrome P450 and eicosanoid metabolism. Cell Mol Life Sci, 59(5), 780-9, 2002

Capdevila, Jorge H, Falck, John R. Biochemical and molecular properties of the cytochrome P450 arachidonic acid monooxygenases. Prostaglandins Other Lipid Mediat, 68-69, 325-44, 2002

Chen, Jian-Kang, Capdevila, Jorge, Harris, Raymond C. Heparin-binding EGF-like growth factor mediates the biological effects of P450 arachidonate epoxygenase metabolites in epithelial cells. Proc Natl Acad Sci U S A, 99(9), 6029-34, 2002 PMCID:122896

Cowart, L Ashley, Wei, Shouzuo, Hsu, Mei-Hui, Johnson, Eric F, Krishna, Murali U, Falck, John R, Capdevila, Jorge H. The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J Biol Chem, 277(38), 35105-12, 2002

Capdevila, J H, Falck, J R. The CYP P450 arachidonic acid monooxygenases: from cell signaling to blood pressure regulation. Biochem Biophys Res Commun, 285(3), 571-6, 2001

Chen, J K, Capdevila, J, Harris, R C. Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Mol Cell Biol, 21(18), 6322-31, 2001 PMCID:87364

Cowart, L A, Falck, J R, Capdevila, J H. Structural determinants of active site binding affinity and metabolism by cytochrome P450 BM-3. Arch Biochem Biophys, 387(1), 117-24, 2001

Holla, V R, Adas, F, Imig, J D, Zhao, X, Price, E, Olsen, N, Kovacs, W J, Magnuson, M A, Keeney, D S, Breyer, M D, Falck, J R, Waterman, M R, Capdevila, J H. Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension. Proc Natl Acad Sci U S A, 98(9), 5211-6, 2001 PMCID:33189

Imig, J.D., Zhao, X., Falck, J.R., Wei, S., and Capdevila, J.H. Enhanced renal microvascular reactivity to angiotensin II in hypertension is ameliorated by the sulfonimide analog of 11,12-epoxyeicosatrienoic acid. J. Hypertens., 19, 983-992, 2001

Mohapatra, S., Capdevila, J.H., Murphy, R.C., Hevko, J.M., and Falck, J. Efficient total synthesis of 5-oxo-6(E),8(Z),14(Z)-eicosatetraenoic acid (5-oxo-ETE), a potent proinflammatory autocoid. Tet. Letts., 42, 4109-4110, 2001

Capdevila, J H, Falck, J R. Biochemical and molecular characteristics of the cytochrome P450 arachidonic acid monooxygenase. Prostaglandins Other Lipid Mediat, 62(3), 271-92, 2000

Capdevila, J H, Falck, J R, Harris, R C. Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J Lipid Res, 41(2), 163-81, 2000

Chen, J K, Capdevila, J, Harris, R C. Overexpression of C-terminal Src kinase blocks 14, 15-epoxyeicosatrienoic acid-induced tyrosine phosphorylation and mitogenesis. J Biol Chem, 275(18), 13789-92, 2000

Falck, J.R., Krishna, M.U., and Capdevila, J.H. Preparation of L--phosphatidyl-D-myo-inositol 3-phosphate (3-PIP) and 3,5-bisphosphate (3,5-PIP2). Biorg. Med. Chem. Lett., 10, 1711-1713, 2000

Helvig, C, Capdevila, J H. Biochemical characterization of rat P450 2C11 fused to rat or bacterial NADPH-P450 reductase domains. Biochemistry, 39(17), 5196-205, 2000

Chen, J K, Wang, D W, Falck, J R, Capdevila, J, Harris, R C. Transfection of an active cytochrome P450 arachidonic acid epoxygenase indicates that 14,15-epoxyeicosatrienoic acid functions as an intracellular second messenger in response to epidermal growth factor. J Biol Chem, 274(8), 4764-9, 1999

Chen, J., Capdevila, J.H., Zeldin, D.C., and Rosenberg, R.L. Inhibition of L-type channels by epoxyeicosatrienoic acids. Mol. Pharmacol., 55, 288-295, 1999

Falck, J.R., Krishna, U., and Capdevila, J.H. A synthesis of L--phosphatidyl-D-myo-inositol 4,5-bisphosphate (4,5-PIP2) and glyceryl lipid analogs. Tetrahedron Lett., 40, 8771-8774, 1999

Holla, V R, Makita, K, Zaphiropoulos, P G, Capdevila, J H. The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading. J Clin Invest, 104(6), 751-60, 1999 PMCID:408434

Chen, J K, Falck, J R, Reddy, K M, Capdevila, J, Harris, R C. Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells. J Biol Chem, 273(44), 29254-61, 1998

Helvig, C, Dishman, E, Capdevila, J H. Molecular, enzymatic, and regulatory characterization of rat kidney cytochromes P450 4A2 and 4A3. Biochemistry, 37(36), 12546-58, 1998

Keeney, D S, Skinner, C, Travers, J B, Capdevila, J H, Nanney, L B, King, L E, Waterman, M R. Differentiating keratinocytes express a novel cytochrome P450 enzyme, CYP2B19, having arachidonate monooxygenase activity. J Biol Chem, 273(48), 32071-9, 1998

Graham-Lorence, S., Truan, G., Peterson, J.A., Falck, J.R., Wei, S., Helvig, C., and Capdevila, J.H. An active site substitution, F87V, converts cytochrome P450 BM-3 into a regio- and stereoselective 14(S), 15(R)-arachidonic acid epoxygenase. J. Biol. Chem., 272, 1127-1135, 1997

Reddy, K.K., Ye, J., Falck, J.R., and Capdevila, J.H. Intracellular second messengers: Synthesis of L-a-phosphatidyl-D-myo-inositol 3,4-bisphosphate and analogs. Bioorganic and Medicinal Chemistry Letters, 7, 2115-2116, 1997

Capdevila, J H, Wei, S, Helvig, C, Falck, J R, Belosludtsev, Y, Truan, G, Graham-Lorence, S E, Peterson, J A. The highly stereoselective oxidation of polyunsaturated fatty acids by cytochrome P450BM-3. J Biol Chem, 271(37), 22663-71, 1996

Makita, K, Falck, J R, Capdevila, J H. Cytochrome P450, the arachidonic acid cascade, and hypertension: new vistas for an old enzyme system. FASEB J, 10(13), 1456-63, 1996

Brash, A R, Boeglin, W E, Capdevila, J H, Yeola, S, Blair, I A. 7-HETE, 10-HETE, and 13-HETE are major products of NADPH-dependent arachidonic acid metabolism in rat liver microsomes: analysis of their stereochemistry, and the stereochemistry of their acid-catalyzed rearrangement. Arch Biochem Biophys, 321(2), 485-92, 1995

Burns, K D, Capdevila, J, Wei, S, Breyer, M D, Homma, T, Harris, R C. Role of cytochrome P-450 epoxygenase metabolites in EGF signaling in renal proximal tubule. Am J Physiol, 269(4 Pt 1), C831-40, 1995

Capdevila, J H, Morrow, J D, Belosludtsev, Y Y, Beauchamp, D R, DuBois, R N, Falck, J R. The catalytic outcomes of the constitutive and the mitogen inducible isoforms of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase(s). Biochemistry, 34(10), 3325-37, 1995

Heckman, B., Mioskoski, C., Sun-Lumin, Falck, J.R., Wei, S., and Capdevila, J.H. Chiral acetals: Stereocontrolled synthesis of 16-, 17- and 18-hydroxyeicosatetraenoic acids, cytochrome P450 arachidonate metabolites. Tetrahedron Lett., 37, 1425-1428, 1995

Sakairi, Y, Jacobson, H R, Noland, T D, Capdevila, J H, Falck, J R, Breyer, M D. 5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis. Am J Physiol, 268(5 Pt 2), F931-9, 1995

Zeldin, D C, DuBois, R N, Falck, J R, Capdevila, J H. Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform. Arch Biochem Biophys, 322(1), 76-86, 1995

Zeldin, D C, Plitman, J D, Kobayashi, J, Miller, R F, Snapper, J R, Falck, J R, Szarek, J L, Philpot, R M, Capdevila, J H. The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance. J Clin Invest, 95(5), 2150-60, 1995 PMCID:295817

Zeldin, D C, Wei, S, Falck, J R, Hammock, B D, Snapper, J R, Capdevila, J H. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. Arch Biochem Biophys, 316(1), 443-51, 1995

Makita, K, Takahashi, K, Karara, A, Jacobson, H R, Falck, J R, Capdevila, J H. Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. J Clin Invest, 94(6), 2414-20, 1994 PMCID:330072

Karara, A, Makita, K, Jacobson, H R, Falck, J R, Guengerich, F P, DuBois, R N, Capdevila, J H. Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase. J Biol Chem, 268(18), 13565-70, 1993

Takahashi, K, Harris, R C, Capdevila, J H, Karara, A, Makita, K, Jacobson, H R, Munger, K A, Badr, K F. Induction of renal arachidonate cytochrome P-450 epoxygenase after uninephrectomy: counterregulation of hyperfiltration. J Am Soc Nephrol, 3(8), 1496-500, 1993

Zeldin, D C, Kobayashi, J, Falck, J R, Winder, B S, Hammock, B D, Snapper, J R, Capdevila, J H. Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. J Biol Chem, 268(9), 6402-7, 1993

Capdevila, J H, Falck, J R, Estabrook, R W. Cytochrome P450 and the arachidonate cascade. FASEB J, 6(2), 731-6, 1992

Capdevila, J H, Wei, S, Kumar, A, Kobayashi, J, Snapper, J R, Zeldin, D C, Bhatt, R K, Falck, J R. Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography. Anal Biochem, 207(2), 236-40, 1992

Capdevila, J H, Wei, S, Yan, J, Karara, A, Jacobson, H R, Falck, J R, Guengerich, F P, DuBois, R N. Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal epoxygenase by dietary salt loading. J Biol Chem, 267(30), 21720-6, 1992

Jajoo, H K, Capdevila, J H, Falck, J R, Bhatt, R K, Blair, I A. Metabolism of 12(R)-hydroxyeicosatetraenoic acid by rat liver microsomes. Biochim Biophys Acta, 1123(1), 110-6, 1992

Karara, A, Wei, S, Spady, D, Swift, L, Capdevila, J H, Falck, J R. Arachidonic acid epoxygenase: structural characterization and quantification of epoxyeicosatrienoates in plasma. Biochem Biophys Res Commun, 182(3), 1320-5, 1992

Karara, A, Dishman, E, Falck, J R, Capdevila, J H. Endogenous epoxyeicosatrienoyl-phospholipids. A novel class of cellular glycerolipids containing epoxidized arachidonate moieties. J Biol Chem, 266(12), 7561-9, 1991

Katoh, T, Takahashi, K, Capdevila, J, Karara, A, Falck, J R, Jacobson, H R, Badr, K F. Glomerular stereospecific synthesis and hemodynamic actions of 8,9-epoxyeicosatrienoic acid in rat kidney. Am J Physiol, 261(4 Pt 2), F578-86, 1991

Capdevila, J H, Karara, A, Waxman, D J, Martin, M V, Falck, J R, Guenguerich, F P. Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. J Biol Chem, 265(19), 10865-71, 1990

Harris, R C, Homma, T, Jacobson, H R, Capdevila, J. Epoxyeicosatrienoic acids activate Na+/H+ exchange and are mitogenic in cultured rat glomerular mesangial cells. J Cell Physiol, 144(3), 429-37, 1990

Karara, A, Dishman, E, Jacobson, H, Falck, J R, Capdevila, J H. Arachidonic acid epoxygenase. Stereochemical analysis of the endogenous epoxyeicosatrienoic acids of human kidney cortex. FEBS Lett, 268(1), 227-30, 1990

Takahashi, K, Capdevila, J, Karara, A, Falck, J R, Jacobson, H R, Badr, K F. Cytochrome P-450 arachidonate metabolites in rat kidney: characterization and hemodynamic responses. Am J Physiol, 258(4 Pt 2), F781-9, 1990

Hammonds, T D, Blair, I A, Falck, J R, Capdevila, J H. Resolution of epoxyeicosatrienoate enantiomers by chiral phase chromatography. Anal Biochem, 182(2), 300-3, 1989

Karara, A, Dishman, E, Blair, I, Falck, J R, Capdevila, J H. Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase. J Biol Chem, 264(33), 19822-7, 1989

Capdevila, J H, Mosset, P, Yadagiri, P, Lumin, S, Falck, J R. NADPH-dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols. Arch Biochem Biophys, 261(1), 122-33, 1988

Capdevila, J, Gil, L, Orellana, M, Marnett, L J, Mason, J I, Yadagiri, P, Falck, J R. Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism. Arch Biochem Biophys, 261(2), 257-63, 1988


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
05/11/2012