Overexpression of heat shock protein 27 protects against ischaemia/reperfusion-induced cardiac dysfunction via stabilization of troponin I and T
| Author(s) | Xi-Yuan Lu, Le Chen, Xiao-Long Cai, Huang-Tian Yang |
| Journal | Cardiovasc Res, Aug 2008; 79: 500 - 508 |
Method Extract | |
| dual emission | |
Abstract | |
| Aims: Heat shock protein 27 (Hsp27) renders cardioprotection from ischaemia/reperfusion (I/R) injury, but little is known about its role in myofilaments. We proposed that increased expression of Hsp27 may improve post-ischaemic contractile dysfunction by preventing I/R-induced cardiac troponin I (cTnI) and troponin T (cTnT) degradation.
Methods and results: Adenovirus-mediated Hsp27 overexpression improved contractile function in perfused rat hearts subjected to global no-flow I/R (30-min/30-min). Such improvement was further confirmed in Hsp27-overexpressing cardiomyocytes subjected to simulated I/R (20-min/30-min). Moreover, these cells showed restored myofilament response to Ca2+ but not intracellular Ca2+ transients. The protection correlated with attenuation of I/R-induced cTnI and cTnT degradation. Confocal microscopy revealed co-localization of Hsp27 with these proteins. Co-immunoprecipitation and pull-down assays further confirmed that Hsp27 interacted with the COOH-terminus of cTnI and the NH2-terminus of cTnT and that Hsp27 overexpression decreased the interaction between µ-calpain (a protease mediating proteolysis of cTnI and cTnT) and cTnI or cTnT under I/R. Conclusion: The findings reveal a novel role of Hsp27 in the protection of cTnI and cTnT from I/R-induced degradation by preventing their proteolytic cleavage via interacting with these proteins. Such protection may result in restored post-ischaemic myofilament response to Ca2+ and improved post-ischaemic contractile function.
KEYWORDS Heat shock protein 27; Ischaemia/reperfusion; Contraction; Troponin I; Troponin T | |
| Keywords | China, hyperswitch, indo, dual emission |