Cardiovascular Research Advance Access [Accepted Manuscript] published online on April 8, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn091
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Overexpression of Heat Shock Protein 27 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction via Stabilization of Troponin I and T
1 Laboratory of Molecular Cardiology, Institute of Health Sciences (IHS), Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM)
2 Laboratory of Molecular Cardiology, IHS, SJTUSM/SIBS, CAS, Shanghai 200025, China
* Corresponding author: Huang-Tian Yang, MD, PhD, Laboratory of Molecular Cardiology, Institute of Health Sciences, SIBS, CAS & SJTUSM, 225 Chong Qing Nan Rd, Shanghai, 200025, China. Phone/Fax: +86-21-63852593; E-mail: htyang{at}sibs.ac.cn
Aims: Heat shock protein 27 (Hsp27) renders cardioprotection from ischemia/reperfusion (I/R) injury, but little is known about its role in myofilaments. We proposed that increased expression of Hsp27 may improve postischemic 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 colocalization of Hsp27 with these proteins. Coimmunoprecipitation 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.
Conclusions: 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 postischemic myofilament response to Ca2+ and improved postischemic contractile function.
KEYWORDS Heat shock protein 27; Ischemia/reperfusion; Contraction; Troponin I; Troponin T
Time for primary review: 31 days
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