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) All Versions of this Article: 287/3/H1081    most recent 00921.2003v1 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 ISI Web of Science 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 ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Griffin, T. M. Articles by Mestril, R. Search for Related Content PubMed PubMed Citation Articles by Griffin, T. M. Articles by Mestril, R.

Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes

Department of Physiology and the Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153

Submitted 26 September 2003 ; accepted in final form 14 April 2004

Heat shock proteins (HSPs) constitute an endogenous cellular defense mechanism against environmental stresses. In the past few years, studies have shown that overexpression of HSPs can protect cardiac myocytes against ischemia-reperfusion injury. In an attempt to increase the HSPs in cardiac tissue, we used the compound radicicol that activates HSP expression by binding to the HSP 90 kDa (HSP90). HSP90 is the main component of the cytosolic molecular chaperone complex, which has been implicated in the regulation of the heat shock factor 1 (HSF1). HSF1 is responsible for the transcriptional activation of the heat shock genes. In the present study, we show that radicicol induces HSP expression in neonatal rat cardiomyocytes, and this increase in HSPs confers cardioprotection to these cardiomyocytes. We also show that radicicol induction of the HSP and cardioprotection is dependent on the inhibition of HSP90 in cardiomyocytes. These results indicate that modulation of the active HSP90 protein level plays an important role in cardioprotection. Therefore, compounds, such as radicicol and its possible derivatives that inhibit the function of HSP90 in the cell may represent potentially useful cardioprotective agents.

heat shock protein 90; heat shock transcriptional factor 1; molecular chaperones

This article has been cited by other articles:

				V. Ramirez, J. M. Mejia-Vilet, D. Hernandez, G. Gamba, and N. A. Bobadilla Radicicol, a heat shock protein 90 inhibitor, reduces glomerular filtration rate Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1044 - F1051. [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]

				S. D. Coaxum, T. M. Griffin, J. L. Martin, and R. Mestril Influence of PKC-{alpha} overexpression on HSP70 and cardioprotection Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2220 - H2226. [Abstract] [Full Text] [PDF]

				E. H. Miyabara, J. L. Martin, T. M. Griffin, A. S. Moriscot, and R. Mestril Overexpression of inducible 70-kDa heat shock protein in mouse attenuates skeletal muscle damage induced by cryolesioning Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1128 - C1138. [Abstract] [Full Text] [PDF]