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Griffin TM, Valdez TV, Mestril R.
Radicicol activates heat shock protein expression and
cardioprotection in neonatal rat cardiomyocytes.
Am J Physiol Heart Circ Physiol. 2004 Apr 29
Department of Physiology and the Cardiovascular Institute,
Loyola University Medical Center, Maywood, Illinios 60153, USA.
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.
PMID: 15117720
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