Jiang B, Zhang B, Liang P, Chen G, Zhou B, Lv C, Tu Z, Xiao X
Nucleolin Protects the Heart from Ischemia/reperfusion Injury by Upregulating Heat Shock Protein 32.
Cardiovascular Research. 2013 Apr 16;
AIMS: Nucleolin plays important roles in a variety of cellular processes. In this study, we aimed to investigate the role of nucleolin in cardiac ischemia/reperfusion injury.Methods and ResultsWe investigated the expression pattern of nucleolin in hearts subjected to ischemia/reperfusion (I/R), or neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). We found that nucleolin expression was significantly down regulated and the cleaved protein was present, both in vivo and in vitro. Gene transfection and RNA interference approaches were employed in cardiomyocytes to investigate the function of nucleolin. Overexpression of nucleolin was cytoprotective, whereas nucleolin ablation enhanced both hypoxia- and H2O2-induced cardiomyocyte death. Furthermore, transgenic mice with cardiac-specific overexpression of nucleolin were resistant to I/R injury as indicated by decreased cellular necrosis and decreased infarct size. The cardio-protective roles of nucleolin in cardiomyocytes, are attributable to the interaction of nucleolin with the mRNA of Hsp32, resulting in an increase of Hsp32 mRNA stability, and subsequent upregulation of Hsp32 expression. The selective Hsp32 inhibitor, ZnPP, abrograted the cardiac protection mediated by nucleolin. CONCLUSIONS: This study has demonstrated that nucleolin is involved in the regulation of I/R-induced cardiac injury and dysfunction via regulation of Hsp32, and may be a novel therapeutic target for ischemic heart diseases.