HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 19, 15983-15989, May 11, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/19/15983    most recent M100439200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Node, K. Articles by Liao, J. K. Search for Related Content PubMed PubMed Citation Articles by Node, K. Articles by Liao, J. K. Social Bookmarking                      What's this?

Activation of G_s Mediates Induction of Tissue-type Plasminogen Activator Gene Transcription by Epoxyeicosatrienoic Acids^*

Koichi Node, Xiu-Lu Ruan, Jianwu Dai, Shui-Xiang Yang, LeRae Graham^§, Darryl C. Zeldin^§, and James K. Liao^¶

From the Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, the  Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, and the ^§ Laboratory of Pulmonary Pathobiology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 (CYP) epoxygenases that have vasodilatory and anti-inflammatory properties. Here we report that EETs have additional fibrinolytic properties. In vascular endothelial cells, physiological concentrations of EETs, particularly 11,12-EET, or overexpression of the endothelial epoxygenase, CYP2J2, increased tissue plasminogen activator (t-PA) expression by 2.5-fold without affecting plasminogen activator inhibitor-1 expression. This increase in t-PA expression correlated with a 4-fold induction in t-PA gene transcription and a 3-fold increase in t-PA fibrinolytic activity and was blocked by the CYP inhibitor, SKF525A, but not by the calcium-activated potassium channel blocker, charybdotoxin, indicating a mechanism that does not involve endothelial cell hyperpolarization. The t-PA promoter is cAMP-responsive, and induction of t-PA gene transcription by EETs correlated with increases in intracellular cAMP levels and, functionally, with cAMP-driven promoter activity. To determine whether increases in intracellular cAMP levels were due to modulation of guanine nucleotide-binding proteins, we assessed the effects of EETs on G_s and G_i2. Treatment with EETs increased G_s, but not G_i2, GTP-binding activity by 3.5-fold. These findings indicate that EETs possess fibrinolytic properties through the induction of t-PA and suggest that endothelial CYP2J2 may play an important role in regulating vascular hemostasis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				G. Yan, S. Chen, B. You, and J. Sun Activation of sphingosine kinase-1 mediates induction of endothelial cell proliferation and angiogenesis by epoxyeicosatrienoic acids Cardiovasc Res, May 1, 2008; 78(2): 308 - 314. [Abstract] [Full Text] [PDF]

				W. Yang, V. R. Tuniki, S. Anjaiah, J. R. Falck, C. J. Hillard, and W. B. Campbell Characterization of Epoxyeicosatrienoic Acid Binding Site in U937 Membranes Using a Novel Radiolabeled Agonist, 20-125I-14,15-Epoxyeicosa-8(Z)-Enoic Acid J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1019 - 1027. [Abstract] [Full Text] [PDF]

				A. Dhanasekaran, S. K. Gruenloh, J. N. Buonaccorsi, R. Zhang, G. J. Gross, J. R. Falck, P. K. Patel, E. R. Jacobs, and M. Medhora Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H724 - H735. [Abstract] [Full Text] [PDF]

				K. L. Hamilton, L. Lin, Y. Wang, and A. A. Knowlton Effect of ovariectomy on cardiac gene expression: inflammation and changes in SOCS gene expression Physiol Genomics, January 17, 2008; 32(2): 254 - 263. [Abstract] [Full Text] [PDF]

				Q. Ke, Y.-F. Xiao, J. A. Bradbury, J. P. Graves, L. M. DeGraff, J. M. Seubert, and D. C. Zeldin Electrophysiological Properties of Cardiomyocytes Isolated from CYP2J2 Transgenic Mice Mol. Pharmacol., October 1, 2007; 72(4): 1063 - 1073. [Abstract] [Full Text] [PDF]

				G. Irusta, M.J. Murphy, W.D. Perez, and J.D. Hennebold Dynamic expression of epoxyeicosatrienoic acid synthesizing and metabolizing enzymes in the primate corpus luteum Mol. Hum. Reprod., August 1, 2007; 13(8): 541 - 548. [Abstract] [Full Text] [PDF]

				J.-G. Jiang, Y.-G. Ning, C. Chen, D. Ma, Z.-J. Liu, S. Yang, J. Zhou, X. Xiao, X. A. Zhang, M. L. Edin, et al. Cytochrome P450 Epoxygenase Promotes Human Cancer Metastasis Cancer Res., July 15, 2007; 67(14): 6665 - 6674. [Abstract] [Full Text] [PDF]

				S. Yang, L. Lin, J.-X. Chen, C. R. Lee, J. M. Seubert, Y. Wang, H. Wang, Z.-R. Chao, D.-D. Tao, J.-P. Gong, et al. Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-{alpha} via MAPK and PI3K/Akt signaling pathways Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H142 - H151. [Abstract] [Full Text] [PDF]

				W. Yang, B. B. Holmes, V. R. Gopal, R. V. K. Kishore, B. Sangras, X.-Y. Yi, J. R. Falck, and W. B. Campbell Characterization of 14,15-Epoxyeicosatrienoyl-Sulfonamides as 14,15-Epoxyeicosatrienoic Acid Agonists: Use for Studies of Metabolism and Ligand Binding J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1023 - 1031. [Abstract] [Full Text] [PDF]

				A. A. Spector and A. W. Norris Action of epoxyeicosatrienoic acids on cellular function Am J Physiol Cell Physiol, March 1, 2007; 292(3): C996 - C1012. [Abstract] [Full Text] [PDF]

				W. B. Campbell and J. R. Falck Arachidonic Acid Metabolites as Endothelium-Derived Hyperpolarizing Factors Hypertension, March 1, 2007; 49(3): 590 - 596. [Abstract] [Full Text] [PDF]

				A. Luria, S. M. Weldon, A. K. Kabcenell, R. H. Ingraham, D. Matera, H. Jiang, R. Gill, C. Morisseau, J. W. Newman, and B. D. Hammock Compensatory Mechanism for Homeostatic Blood Pressure Regulation in Ephx2 Gene-disrupted Mice J. Biol. Chem., February 2, 2007; 282(5): 2891 - 2898. [Abstract] [Full Text] [PDF]

				J. M. Seubert, C. J. Sinal, J. Graves, L. M. DeGraff, J. A. Bradbury, C. R. Lee, K. Goralski, M. A. Carey, A. Luria, J. W. Newman, et al. Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile Function Circ. Res., August 18, 2006; 99(4): 442 - 450. [Abstract] [Full Text] [PDF]

				A. Dhanasekaran, R. Al-Saghir, B. Lopez, D. Zhu, D. D. Gutterman, E. R. Jacobs, and M. Medhora Protective effects of epoxyeicosatrienoic acids on human endothelial cells from the pulmonary and coronary vasculature Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H517 - H531. [Abstract] [Full Text] [PDF]

				M. A. Carroll, A. B. Doumad, J. Li, M. K. Cheng, J. R. Falck, and J. C. McGiff Adenosine2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway Am J Physiol Renal Physiol, July 1, 2006; 291(1): F155 - F161. [Abstract] [Full Text] [PDF]

				C. R. Lee, K. E. North, M. S. Bray, M. Fornage, J. M. Seubert, J. W. Newman, B. D. Hammock, D. J. Couper, G. Heiss, and D. C. Zeldin Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study Hum. Mol. Genet., May 15, 2006; 15(10): 1640 - 1649. [Abstract] [Full Text] [PDF]

				Z. Yu, V. Y. Ng, P. Su, M. M. Engler, M. B. Engler, Y. Huang, E. Lin, and D. L. Kroetz Induction of Renal Cytochrome P450 Arachidonic Acid Epoxygenase Activity by Dietary {gamma}-Linolenic Acid J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 732 - 738. [Abstract] [Full Text] [PDF]

				D. Ye, W. Zhou, T. Lu, S. G. Jagadeesh, J. R. Falck, and H.-C. Lee Mechanism of rat mesenteric arterial KATP channel activation by 14,15-epoxyeicosatrienoic acid Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1326 - H1336. [Abstract] [Full Text] [PDF]

				A. A. Elmarakby, J. E. Quigley, D. M. Pollock, and J. D. Imig Tumor Necrosis Factor {alpha} Blockade Increases Renal Cyp2c23 Expression and Slows the Progression of Renal Damage in Salt-Sensitive Hypertension Hypertension, March 1, 2006; 47(3): 557 - 562. [Abstract] [Full Text] [PDF]

				W. B. Campbell, B. B. Holmes, J. R. Falck, J. H. Capdevila, and K. M. Gauthier Regulation of potassium channels in coronary smooth muscle by adenoviral expression of cytochrome P-450 epoxygenase Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H64 - H71. [Abstract] [Full Text] [PDF]

				J. D. Imig Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases Am J Physiol Renal Physiol, September 1, 2005; 289(3): F496 - F503. [Abstract] [Full Text] [PDF]

				E. L. Liclican, J. C. McGiff, P. L. Pedraza, N. R. Ferreri, J. R. Falck, and M. A. Carroll Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic acids Am J Physiol Renal Physiol, August 1, 2005; 289(2): F386 - F392. [Abstract] [Full Text] [PDF]

				U. R. Michaelis, J. R. Falck, R. Schmidt, R. Busse, and I. Fleming Cytochrome P4502C9-Derived Epoxyeicosatrienoic Acids Induce the Expression of Cyclooxygenase-2 in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 321 - 326. [Abstract] [Full Text] [PDF]

				Y.-F. Xiao, Q. Ke, J. M. Seubert, J. A. Bradbury, J. Graves, L. M. DeGraff, J. R. Falck, K. Krausz, H. V. Gelboin, J. P. Morgan, et al. Enhancement of Cardiac L-Type Ca2+ Currents in Transgenic Mice with Cardiac-Specific Overexpression of CYP2J2 Mol. Pharmacol., December 1, 2004; 66(6): 1607 - 1616. [Abstract] [Full Text] [PDF]

				X. Fang, N. L. Weintraub, R. B. McCaw, S. Hu, S. D. Harmon, J. B. Rice, B. D. Hammock, and A. A. Spector Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2412 - H2420. [Abstract] [Full Text] [PDF]

				J. W. Newman, J. E. Stok, J. D. Vidal, C. J. Corbin, Q. Huang, B. D. Hammock, and A. J. Conley Cytochrome P450-Dependent Lipid Metabolism in Preovulatory Follicles Endocrinology, November 1, 2004; 145(11): 5097 - 5105. [Abstract] [Full Text] [PDF]

				M. Spiecker, H. Darius, T. Hankeln, M. Soufi, A. M. Sattler, J. R. Schaefer, K. Node, J. Borgel, A. Mugge, K. Lindpaintner, et al. Risk of Coronary Artery Disease Associated With Polymorphism of the Cytochrome P450 Epoxygenase CYP2J2 Circulation, October 12, 2004; 110(15): 2132 - 2136. [Abstract] [Full Text] [PDF]

				X. Zhao, T. Yamamoto, J. W. Newman, I.-H. Kim, T. Watanabe, B. D. Hammock, J. Stewart, J. S. Pollock, D. M. Pollock, and J. D. Imig Soluble Epoxide Hydrolase Inhibition Protects the Kidney from Hypertension-Induced Damage J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1244 - 1253. [Abstract] [Full Text] [PDF]

				J. D. Imig ACE Inhibition and Bradykinin-Mediated Renal Vascular Responses: EDHF Involvement Hypertension, March 1, 2004; 43(3): 533 - 535. [Full Text] [PDF]

				H. Wang, L. Lin, J. Jiang, Y. Wang, Z. Y. Lu, J. A. Bradbury, F. B. Lih, D. W. Wang, and D. C. Zeldin Up-Regulation of Endothelial Nitric-Oxide Synthase by Endothelium-Derived Hyperpolarizing Factor Involves Mitogen-Activated Protein Kinase and Protein Kinase C Signaling Pathways J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 753 - 764. [Abstract] [Full Text] [PDF]

				Y. Zhu and D. Y. Hui Apolipoprotein E Binding to Low Density Lipoprotein Receptor-related Protein-1 Inhibits Cell Migration via Activation of cAMP-dependent Protein Kinase A J. Biol. Chem., September 19, 2003; 278(38): 36257 - 36263. [Abstract] [Full Text] [PDF]

				M. Potente, B. Fisslthaler, R. Busse, and I. Fleming 11,12-Epoxyeicosatrienoic Acid-induced Inhibition of FOXO Factors Promotes Endothelial Proliferation by Down-Regulating p27Kip1 J. Biol. Chem., August 8, 2003; 278(32): 29619 - 29625. [Abstract] [Full Text] [PDF]

				T. Matsumoto, K. Minai, H. Horie, N. Ohira, H. Takashima, Y. Tarutani, Y. o Yasuda, T. Ozawa, S. Matsuo, M. Kinoshita, et al. Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1373 - 1379. [Abstract] [Full Text] [PDF]

				X. Fang, N. L. Weintraub, C. L. Oltman, L. L. Stoll, T. L. Kaduce, S. Harmon, K. C. Dellsperger, C. Morisseau, B. D. Hammock, and A. A. Spector Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2306 - H2314. [Abstract] [Full Text] [PDF]

				G. D. Snyder, U. M. Krishna, J. R. Falck, and A. A. Spector Evidence for a membrane site of action for 14,15-EET on expression of aromatase in vascular smooth muscle Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1936 - H1942. [Abstract] [Full Text] [PDF]

				N. J. Alkayed, T. Goyagi, H.-D. Joh, J. Klaus, D. R. Harder, R. J. Traystman, and P. D. Hurn Neuroprotection and P450 2C11 Upregulation After Experimental Transient Ischemic Attack Stroke, June 1, 2002; 33(6): 1677 - 1684. [Abstract] [Full Text] [PDF]

				I. Fleming To Move or Not To Move?: Cytochrome P450 Products and Cell Migration Circ. Res., May 17, 2002; 90(9): 936 - 938. [Full Text] [PDF]

				J. Sun, X. Sui, J. A. Bradbury, D. C. Zeldin, M. S. Conte, and J. K. Liao Inhibition of Vascular Smooth Muscle Cell Migration by Cytochrome P450 Epoxygenase-Derived Eicosanoids Circ. Res., May 17, 2002; 90(9): 1020 - 1027. [Abstract] [Full Text] [PDF]

				L. M. King, J. Ma, S. Srettabunjong, J. Graves, J. A. Bradbury, L. Li, M. Spiecker, J. K. Liao, H. Mohrenweiser, and D. C. Zeldin Cloning of CYP2J2 Gene and Identification of Functional Polymorphisms Mol. Pharmacol., April 1, 2002; 61(4): 840 - 852. [Abstract] [Full Text] [PDF]

				B. Yang, L. Graham, S. Dikalov, R. P. Mason, J. R. Falck, J. K. Liao, and D. C. Zeldin Overexpression of Cytochrome P450 CYP2J2 Protects against Hypoxia-Reoxygenation Injury in Cultured Bovine Aortic Endothelial Cells Mol. Pharmacol., August 1, 2001; 60(2): 310 - 320. [Abstract] [Full Text] [PDF]

				D. C. Zeldin Epoxygenase Pathways of Arachidonic Acid Metabolism J. Biol. Chem., September 21, 2001; 276(39): 36059 - 36062. [Full Text] [PDF]