Hypoxia/reoxygenation causes cell death of cardiomyocytes by a mitochondrion-dependent pathway. The Ca2+/CaM activated FK506-binding protein 38 (FKBP38) can interact with Bcl-2 through its PPIase active site and promotes apoptosis. This study investigated the effect of specific FKBP38 inhibition with DM- CHX on the hypoxia/reoxygenation-induced apoptosis. Ventricular myocytes from adult or neonatal rates were cultured and subjected to hypoxic conditions (0.2% O2) for 18 or 24 hrs (adult/neonatal) followed by a reoxygenation period (21% O2) of 24 hrs. Apoptotic cell analysis was determined by using the ViaCount assay (Guava Technologies). In adult myocytes, hypoxia caused 34% and hypoxia/reoxygenation 31% apoptotic cells. DM-CHX (5mM) resulted in 22% (hypoxia) and 11% (hypoxia/reoxygenation) apoptotic cells. In neonatal myocytes, under both conditions 64% apoptotic cells were analysed, reduced to 34% after DM-CHX (5 mM) treatment. As positive control, caspase-inhibiton and cyclosporin A showed apoptosis inhibition in both types of myocytes. Our results suggest that DM-CHX, a specific inhibitor of FKBP38, reduces apoptosis in cardiomyocytes in a dose-dependent manner. Such a specific drug could be used to decrease the loss of myocytes after damaged injury resulting in an improved cardiac function.

Cooperation with Max-Planck Research Unit for Enzymology of Protein Folding, Halle