Effect of a low dose of proteasome inhibitor on cell death and gene expression in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation.
BACKGROUND
Recent data suggest that low concentrations of proteasome inhibitors (PIs) are cytoprotective in models of ischemia-reperfusion injury, but the underlying mechanisms of this effect still remain unclear.


OBJECTIVE
To investigate the effect of 100 nM of clasto-lactacystin beta-lactone on cell death and gene expression in neonatal rat cardiomyocytes exposed to anoxia-reoxygenation.


METHODS
Fluorescent microscopy and real-time polymerase chain reaction were used to detect different types of cell death and gene expression, respectively, in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation.


RESULTS
It was shown that a low dose of clasto-lactacystin beta-lactone protected the cells against anoxia-reoxygenation injury by a reduction in the number of necrotic and apoptotic cells. The number of autophagic cells was greatly increased by proteasomal inhibition. The PI increased the heat shock protein 70 messenger RNA expression twofold and slightly reduced the expression of heat shock protein 90 gene. The expression of the FK506 binding protein 12-rapamycin associated protein gene was increased 1.57-fold on PI application. The B-cell lymphoma 2 gene expression was unaffected by the use of clasto-lactacystin beta-lactone in low dose.


CONCLUSIONS
Although PIs are injurious, they may be cardioprotective in low doses; ie, they do not result in cell death. Moreover, PIs initiate the protective mechanisms that prevent cell damage by changing the expression of several genes.
Surova
Olga V
OV
Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kiev, Ukraine.
Nagibin
Vasyl S
VS
Tumanovskaya
Lesya V
LV
Dosenko
Victor E
VE
Moibenko
Alexey A
AA
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