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

J. Biol. Chem., Vol. 281, Issue 23, 16128-16138, June 9, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/23/16128    most recent M508810200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frey, R. S. Articles by Malik, A. B. Search for Related Content PubMed PubMed Citation Articles by Frey, R. S. Articles by Malik, A. B. Social Bookmarking                      What's this?

Phosphatidylinositol 3-Kinase Signaling through Protein Kinase C Induces NADPH Oxidase-mediated Oxidant Generation and NF-B Activation in Endothelial Cells^*

Randall S. Frey¹, Xiaopei Gao, Kamran Javaid, Shahid S. Siddiqui, Arshad Rahman, and Asrar B. Malik

From the Department of Pharmacology and Center for Lung and Vascular Biology, the University of Illinois College of Medicine, Chicago, Illinois 60612 and the Departments of Pediatrics and Environmental Medicine, University of Rochester School of Medicine, Rochester, New York 14642

We addressed the role of class 1B phosphatidylinositol 3-kinase (PI3K) isoform PI3K in mediating NADPH oxidase activation and reactive oxidant species (ROS) generation in endothelial cells (ECs) and of PI3K-mediated oxidant signaling in the mechanism of NF-B activation and intercellular adhesion molecule (ICAM)-1 expression. We used lung microvascular ECs isolated from mice with targeted deletion of the p110 catalytic subunit of PI3K. Tumor necrosis factor (TNF) challenge of wild type ECs caused p110 translocation to the plasma membrane and phosphatidylinositol 1,4,5-trisphosphate production coupled to ROS production; however, this response was blocked in p110^–/– ECs. ROS production was the result of TNF activation of Ser phosphorylation of NADPH oxidase subunit p47^phox and its translocation to EC membranes. NADPH oxidase activation failed to occur in p110^–/– ECs. Additionally, the TNF-activated NF-B binding to the ICAM-1 promoter, ICAM-1 protein expression, and PMN adhesion to ECs required functional PI3K. TNF challenge of p110^–/– ECs failed to induce phosphorylation of PDK1 and activation of the atypical PKC isoform, PKC. Thus, PI3K lies upstream of PKC in the endothelium, and its activation is crucial in signaling NADPH oxidase-dependent oxidant production and subsequent NF-B activation and ICAM-1 expression.

Received for publication, August 10, 2005 , and in revised form, February 21, 2006.

^* This work was supported in part by National Institutes of Health Grants T32 HL07239 and HL60678 (to A. B. M.) and HL67424 (to A. R.) and a research grant from the American Lung Association (to R. S. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Pharmacology, University of Illinois College of Medicine, 835 S. Wolcott Ave., E403, Chicago, IL 60612. Tel.: 312-413-3428; Fax: 312-996-1225; E-mail. RFrey{at}uic.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Huang, L.-Y. Chen, A. M. Doerner, W. W. Pan, L. Smith, S. Huang, T. J. Papadimos, and Z. K. Pan An Atypical Protein Kinase C (PKC{zeta}) Plays a Critical Role in Lipopolysaccharide-Activated NF-{kappa}B in Human Peripheral Blood Monocytes and Macrophages J. Immunol., May 1, 2009; 182(9): 5810 - 5815. [Abstract] [Full Text] [PDF]

				A. Espinosa, A. Garcia, S. Hartel, C. Hidalgo, and E. Jaimovich NADPH Oxidase and Hydrogen Peroxide Mediate Insulin-induced Calcium Increase in Skeletal Muscle Cells J. Biol. Chem., January 23, 2009; 284(4): 2568 - 2575. [Abstract] [Full Text] [PDF]

				L. Xia, H. Wang, S. Munk, J. Kwan, H. J. Goldberg, I. G. Fantus, and C. I. Whiteside High glucose activates PKC-{zeta} and NADPH oxidase through autocrine TGF-{beta}1 signaling in mesangial cells Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1705 - F1714. [Abstract] [Full Text] [PDF]

				R. Heller, Q. Chang, G. Ehrlich, S. N. Hsieh, S. M. Schoenwaelder, P. J. Kuhlencordt, K. T. Preissner, E. Hirsch, and R. Wetzker Overlapping and distinct roles for PI3K{beta} and {gamma} isoforms in S1P-induced migration of human and mouse endothelial cells Cardiovasc Res, October 1, 2008; 80(1): 96 - 105. [Abstract] [Full Text] [PDF]

				Y. Kim, Y.-S. Lee, J. Choe, H. Lee, Y.-M. Kim, and D. Jeoung CD44-Epidermal Growth Factor Receptor Interaction Mediates Hyaluronic Acid-promoted Cell Motility by Activating Protein Kinase C Signaling Involving Akt, Rac1, Phox, Reactive Oxygen Species, Focal Adhesion Kinase, and MMP-2 J. Biol. Chem., August 15, 2008; 283(33): 22513 - 22528. [Abstract] [Full Text] [PDF]

				N. Urao, H. Inomata, M. Razvi, H. W. Kim, K. Wary, R. McKinney, T. Fukai, and M. Ushio-Fukai Role of Nox2-Based NADPH Oxidase in Bone Marrow and Progenitor Cell Function Involved in Neovascularization Induced by Hindlimb Ischemia Circ. Res., July 18, 2008; 103(2): 212 - 220. [Abstract] [Full Text] [PDF]

				L. Moreno, G. Frazziano, A. Cogolludo, L. Cobeno, J. Tamargo, and F. Perez-Vizcaino Role of Protein Kinase C{zeta} and Its Adaptor Protein p62 in Voltage-Gated Potassium Channel Modulation in Pulmonary Arteries Mol. Pharmacol., November 1, 2007; 72(5): 1301 - 1309. [Abstract] [Full Text] [PDF]

				P. V. Usatyuk, L. H. Romer, D. He, N. L. Parinandi, M. E. Kleinberg, S. Zhan, J. R. Jacobson, S. M. Dudek, S. Pendyala, J. G. N. Garcia, et al. Regulation of Hyperoxia-induced NADPH Oxidase Activation in Human Lung Endothelial Cells by the Actin Cytoskeleton and Cortactin J. Biol. Chem., August 10, 2007; 282(32): 23284 - 23295. [Abstract] [Full Text] [PDF]

				G. Y. Oudit, Z. Kassiri, M. P. Patel, M. Chappell, J. Butany, P. H. Backx, R. G. Tsushima, J. W. Scholey, R. Khokha, and J. M. Penninger Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice Cardiovasc Res, July 1, 2007; 75(1): 29 - 39. [Abstract] [Full Text] [PDF]

				Y. Anini, A. Izzo, G. Y. Oudit, P. H. Backx, and P. L. Brubaker Role of phosphatidylinositol-3 kinase-{gamma} in the actions of glucagon-like peptide-2 on the murine small intestine Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1599 - E1606. [Abstract] [Full Text] [PDF]

				S. S. Singhal, J. Singhal, S. Yadav, S. Dwivedi, P. J. Boor, Y. C. Awasthi, and S. Awasthi Regression of Lung and Colon Cancer Xenografts by Depleting or Inhibiting RLIP76 (Ral-Binding Protein 1) Cancer Res., May 1, 2007; 67(9): 4382 - 4389. [Abstract] [Full Text] [PDF]

				X.-P. Gao, X. Zhu, J. Fu, Q. Liu, R. S. Frey, and A. B. Malik Blockade of Class IA Phosphoinositide 3-Kinase in Neutrophils Prevents NADPH Oxidase Activation- and Adhesion-dependent Inflammation J. Biol. Chem., March 2, 2007; 282(9): 6116 - 6125. [Abstract] [Full Text] [PDF]

				K. Krishnamurthy, G. Wang, J. Silva, B. G. Condie, and E. Bieberich Ceramide Regulates Atypical PKC{zeta}/{lambda}-mediated Cell Polarity in Primitive Ectoderm Cells: A NOVEL FUNCTION OF SPHINGOLIPIDS IN MORPHOGENESIS J. Biol. Chem., February 2, 2007; 282(5): 3379 - 3390. [Abstract] [Full Text] [PDF]

				C. F. Fortin, O. Lesur, and T. Fulop Jr Effects of TREM-1 activation in human neutrophils: activation of signaling pathways, recruitment into lipid rafts and association with TLR4 Int. Immunol., January 1, 2007; 19(1): 41 - 50. [Abstract] [Full Text] [PDF]