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

J. Biol. Chem., Vol. 280, Issue 27, 25350-25360, July 8, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/27/25350    most recent M503512200v1 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 Taillé, C. Articles by Motterlini, R. Search for Related Content PubMed PubMed Citation Articles by Taillé, C. Articles by Motterlini, R. Social Bookmarking                      What's this?

Mitochondrial Respiratory Chain and NAD(P)H Oxidase Are Targets for the Antiproliferative Effect of Carbon Monoxide in Human Airway Smooth Muscle^*

Camille Taillé, Jamel El-Benna, Sophie Lanone, Jorge Boczkowski¶, and Roberto Motterlini||

From the INSERM Unité 700 and Unité 683, Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, 75018 Paris, France and the^|| Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex HA1 3UJ, United Kingdom

Carbon monoxide (CO), one of the end products of heme oxygenase activity, inhibits smooth muscle proliferation by decreasing ERK1/2 phosphorylation and cyclin D1 expression, a signaling pathway that is known to be modulated by reactive oxygen species (ROS) in airway smooth muscle cells (ASMCs). Two important sources of ROS involved in cell signaling are the membrane NAD(P)H oxidase and the mitochondrial respiratory chain. Thus, that CO could modulate redox signaling in ASMCs by interacting with the heme moiety of NAD(P)H oxidase and/or the respiratory chain is a plausible hypothesis. Here we show that a recently identified carbon monoxide-releasing molecule, [Ru(CO)₃Cl₂]₂ (or CORM-2) 1) inhibits NAD(P)H oxidase cytochrome b₅₅₈ activity, 2) increases oxidant production by the mitochondria, and 3) inhibits ASMC proliferation and phosphorylation of the ERK1/2 mitogen-activated protein kinase and expression of cyclin D1, two critical pathways involved in muscle proliferation. No such effects were observed with the negative control (Ru(Me₂SO)₄Cl₂), which does not contain CO groups. Because both diphenylene iodinium or apocynin (inhibitors of NAD(P)H oxidase) and rotenone (a molecule that increases mitochondrial ROS production by blocking the respiratory chain) mimicked the effect of CORM-2 on cyclin D1 expression and ASMC proliferation, the antiproliferative effect of CORM-2 is probably related to inhibition of cytochromes on both NAD(P)H oxidase and the respiratory chain. The involvement of increased mitochondria-derived oxidants is substantiated by the findings showing that the antioxidant N-acetylcysteine partially inhibited the effects of CORM-2. This study provides a new mechanism to explain redox signaling by CO.

Received for publication, March 31, 2005

^* 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.

^¶ To whom correspondence should be addressed: INSERM, Unité 700, Faculté deMédecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France. Tel.: 33-1-44-85-62-50; Fax: 33-1-42-26-33-30; E-mail: jbb2{at}bichat.inserm.fr.

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

This article has been cited by other articles:

				N. G. Innamorato, A. I. Rojo, A. J. Garcia-Yague, M. Yamamoto, M. L. de Ceballos, and A. Cuadrado The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation J. Immunol., July 1, 2008; 181(1): 680 - 689. [Abstract] [Full Text] [PDF]

				H. S. Kim, P. A. Loughran, J. Rao, T. R. Billiar, and B. S. Zuckerbraun Carbon monoxide activates NF-{kappa}B via ROS generation and Akt pathways to protect against cell death of hepatocytes Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G146 - G152. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

				D. E. Stec, H. A. Drummond, and T. Vera Role of Carbon Monoxide in Blood Pressure Regulation Hypertension, March 1, 2008; 51(3): 597 - 604. [Full Text] [PDF]

				S. R. Datla, G. J. Dusting, T. A. Mori, C. J. Taylor, K. D. Croft, and F. Jiang Induction of Heme Oxygenase-1 In Vivo Suppresses NADPH Oxidase Derived Oxidative Stress Hypertension, October 1, 2007; 50(4): 636 - 642. [Abstract] [Full Text] [PDF]

				M.-H. Li, J.-H. Jang, H.-K. Na, Y.-N. Cha, and Y.-J. Surh Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling J. Biol. Chem., September 28, 2007; 282(39): 28577 - 28586. [Abstract] [Full Text] [PDF]

				Y. Y. Sautin, T. Nakagawa, S. Zharikov, and R. J. Johnson Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress Am J Physiol Cell Physiol, August 1, 2007; 293(2): C584 - C596. [Abstract] [Full Text] [PDF]

				N. Amara, R. Bachoual, M. Desmard, S. Golda, C. Guichard, S. Lanone, M. Aubier, E. Ogier-Denis, and J. Boczkowski Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L170 - L181. [Abstract] [Full Text] [PDF]

				B. S. Zuckerbraun, B. Y. Chin, M. Bilban, J. de Costa d'Avila, J. Rao, T. R. Billiar, and L. E. Otterbein Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species FASEB J, April 1, 2007; 21(4): 1099 - 1106. [Abstract] [Full Text] [PDF]

				T. Vera, S. Kelsen, L. L. Yanes, J. F. Reckelhoff, and D. E. Stec HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1472 - R1478. [Abstract] [Full Text] [PDF]

				B. Y. Chin, G. Jiang, B. Wegiel, H. J. Wang, T. MacDonald, X. C. Zhang, D. Gallo, E. Cszimadia, F. H. Bach, P. J. Lee, et al. Hypoxia-inducible factor 1{alpha} stabilization by carbon monoxide results in cytoprotective preconditioning PNAS, March 20, 2007; 104(12): 5109 - 5114. [Abstract] [Full Text] [PDF]

				K. Nakahira, H. P. Kim, X. H. Geng, A. Nakao, X. Wang, N. Murase, P. F. Drain, X. Wang, M. Sasidhar, E. G. Nabel, et al. Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts J. Exp. Med., October 2, 2006; 203(10): 2377 - 2389. [Abstract] [Full Text] [PDF]

				P. Sawle, J. Hammad, I. J. S. Fairlamb, B. Moulton, C. T. O'Brien, J. M. Lynam, A. K. Duhme-Klair, R. Foresti, and R. Motterlini Bioactive Properties of Iron-Containing Carbon Monoxide-Releasing Molecules J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 403 - 410. [Abstract] [Full Text] [PDF]

				Y. Tayem, T. R. Johnson, B. E. Mann, C. J. Green, and R. Motterlini Protection against cisplatin-induced nephrotoxicity by a carbon monoxide-releasing molecule Am J Physiol Renal Physiol, April 1, 2006; 290(4): F789 - F794. [Abstract] [Full Text] [PDF]

				A. Galkin and U. Brandt Superoxide Radical Formation by Pure Complex I (NADH:Ubiquinone Oxidoreductase) from Yarrowia lipolytica J. Biol. Chem., August 26, 2005; 280(34): 30129 - 30135. [Abstract] [Full Text] [PDF]

				Q. Xi, S. Y. Cheranov, and J. H. Jaggar Mitochondria-Derived Reactive Oxygen Species Dilate Cerebral Arteries by Activating Ca2+ Sparks Circ. Res., August 19, 2005; 97(4): 354 - 362. [Abstract] [Full Text] [PDF]