Nuclear translocation of calpain-2 regulates propensity toward apoptosis in cardiomyocytes of tail-suspended rats.
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.
Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China.
Hui
H
Chang
Lin
L
Zhang
Peng-Tao
PT
Xu
Quan
Q
Li
Juan-Juan
JJ
Sheng
Yun-Ying
YY
Wang
Yan
Y
Chen
Lan-Ning
LN
Zhang
Zhi-Bin
ZB
Yu
D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000179:Acrylates; C100442:PD 150606; D002154:Calpain; D007545:Isoproterenol; D002118:Calcium