Nuclear translocation of calpain‐2 regulates propensity toward apoptosis in cardiomyocytes of tail‐suspended rats

Abstract The compensatory increase in catecholamine release does not reverse orthostatic intolerance after returning from a long‐term spaceflight, but it is unclear whether high dose of catecholamine induces cardiac damage. The tail‐suspended rat model was used to simulate the effects of weightlessness on the heart. Apoptotic rates in the left ventricular myocardium did not increase in 4‐week of tail‐suspended rats compared with the synchronous control. On the contrary, isoproterenol (intraperitoneal injection) and 1‐day recovery from the 4‐week tail‐suspension increased apoptotic rates in the myocardium. Propranolol and PD150606 inhibited cardiomyocyte apoptosis in the recovery group. PD150606 and calpain‐2 knockdown also blocked isoproterenol‐induced cardiomyocyte apoptosis in tail‐suspended rats. The activity and nuclear translocation of calpain‐2 increased, but the expression of calpain‐1, calpain‐2, and calpastatin was unchanged in the myocardium of tail‐suspended rats. The Ser‐16‐phosphorylated phospholamban of the nuclear envelope was higher in tail‐suspended rats than in the control rats under isoproterenol stimulation. Isoproterenol treatment also induced a large intranuclear Ca 2+ transient of cardiomyocytes in tail‐suspended rats. These results suggest that high‐dose isoproterenol phosphorylates phospholamban of the nuclear envelope and increases intranuclear Ca 2+ transient. Larger intranuclear Ca 2+ further activates nuclear calpain‐2 and hence induces cardiomyocyte apoptosis. J. Cell. Biochem. 112: 571–580, 2011. © 2010 Wiley‐Liss, Inc.