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1 Department of Physiology and the Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois, USA
* To whom correspondence should be addressed. E-mail: rmestri{at}lumc.edu.
The heat shock proteins constitute an endogenous cellular defense mechanism against environmental stresses. In the past few years, studies have shown that overexpression of heat shock proteins (hsp) can protect cardiac myocytes against ischemia-reperfusion injury. In an attempt to increase the heat shock proteins in cardiac tissue, we have used the compound radicicol that activates hsp expression by binding to the heat shock protein 90 kD (hsp90). Hsp90 is the main component of the cytosolic molecular chaperone complex that 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 heat shock proteins confers cardioprotection to these cardiomyocytes. We also show that radicicol induction of the heat shock proteins 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 hsp90's function in the cell may represent potential useful cardioprotective agents.
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