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

This Article Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Kim, H. P. Articles by Choi, A. M. K. Search for Related Content PubMed PubMed Citation Articles by Kim, H. P. Articles by Choi, A. M. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CARBON MONOXIDE

Heat Shock Protein-70 Mediates the Cytoprotective Effect of Carbon Monoxide: Involvement of p38 MAPK and Heat Shock Factor-1 ¹

Hong Pyo Kim^*, Xue Wang^*, Jinglan Zhang^*, Gee Young Suh^*, Ivor J. Benjamin, Stefan W. Ryter^* and Augustine M. K. Choi^2,*

^* Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213; and Department of Internal Medicine, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, UT 84132

Carbon monoxide (CO), a product of heme oxygenase activity, exerts antiapoptotic and anti-inflammatory effects in vitro and in vivo. The anti-inflammatory effects of CO involve the inhibition of TNF- expression and the enhancement of IL-10 production, resulting in reduced mortality after endotoxin challenge. In this study we demonstrate for the first time that the protective effects of CO involve the increased expression of the 70-kDa inducible heat shock protein (Hsp70) in murine lung endothelial cells and fibroblasts. The p38 MAPK mediated the effects of CO on cytoprotection and Hsp70 regulation. Suppression of Hsp70 expression and/or genetic deletion of heat shock factor-1, the principle transcriptional regulator of Hsp70, attenuated the cytoprotective and immunomodulatory effects of CO in mouse lung cells and in vivo. These data provide a novel mechanism for the protective effects of CO and underscore a potential application of this gaseous molecule in anti-inflammatory therapies.

This article has been cited by other articles:

				S. W. Ryter and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Metabolism to Molecular Therapy Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 251 - 260. [Abstract] [Full Text] [PDF]

				U. Goebel, A. Mecklenburg, M. Siepe, M. Roesslein, C. I. Schwer, H. L. Pahl, H. J. Priebe, C. Schlensak, and T. Loop Protective effects of inhaled carbon monoxide in pig lungs during cardiopulmonary bypass are mediated via an induction of the heat shock response Br. J. Anaesth., August 1, 2009; 103(2): 173 - 184. [Abstract] [Full Text] [PDF]

				E. M. Harrison, E. Sharpe, C. O. Bellamy, S. J. McNally, L. Devey, O. J. Garden, J. A. Ross, and S. J. Wigmore Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury Am J Physiol Renal Physiol, August 1, 2008; 295(2): F397 - F405. [Abstract] [Full Text] [PDF]

				G Schett, J Zwerina, and G Firestein The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis Ann Rheum Dis, July 1, 2008; 67(7): 909 - 916. [Abstract] [Full Text] [PDF]

				A. Hoetzel, T. Dolinay, S. Vallbracht, Y. Zhang, H. P. Kim, E. Ifedigbo, S. Alber, A. M. Kaynar, R. Schmidt, S. W. Ryter, et al. Carbon Monoxide Protects against Ventilator-induced Lung Injury via PPAR-{gamma} and Inhibition of Egr-1 Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1223 - 1232. [Abstract] [Full Text] [PDF]

				D. Tang, R. Kang, W. Xiao, H. Wang, S. K. Calderwood, and X. Xiao The Anti-inflammatory Effects of Heat Shock Protein 72 Involve Inhibition of High-Mobility-Group Box 1 Release and Proinflammatory Function in Macrophages J. Immunol., July 15, 2007; 179(2): 1236 - 1244. [Abstract] [Full Text] [PDF]

				S. W. Ryter, D. Morse, and A. M. K. Choi Carbon Monoxide and Bilirubin: Potential Therapies for Pulmonary/Vascular Injury and Disease Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 175 - 182. [Abstract] [Full Text] [PDF]

				S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, C. W. Leffler, and H. Parfenova HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-{alpha} in cerebral vascular endothelial cells Am J Physiol Cell Physiol, November 1, 2006; 291(5): C897 - C908. [Abstract] [Full Text] [PDF]

				G. Silva, A. Cunha, I. P. Gregoire, M. P. Seldon, and M. P. Soares The Antiapoptotic Effect of Heme Oxygenase-1 in Endothelial Cells Involves the Degradation of p38{alpha} MAPK Isoform J. Immunol., August 1, 2006; 177(3): 1894 - 1903. [Abstract] [Full Text] [PDF]

				M. Liu, R. Aneja, C. Liu, L. Sun, J. Gao, H. Wang, J.-T. Dong, V. Sarli, A. Giannis, H. C. Joshi, et al. Inhibition of the Mitotic Kinesin Eg5 Up-regulates Hsp70 through the Phosphatidylinositol 3-Kinase/Akt Pathway in Multiple Myeloma Cells J. Biol. Chem., June 30, 2006; 281(26): 18090 - 18097. [Abstract] [Full Text] [PDF]