title: Nucleolin protects the heart from ischaemia-reperfusion injury by up-regulating heat shock protein 32.
abstract: OBJECTIVE
  Nucleolin plays important roles in a variety of cellular processes. In this study, we aimed to investigate the role of nucleolin in cardiac ischaemia-reperfusion (I-R) injury.
  
  
  RESULTS
  We investigated the expression pattern of nucleolin in hearts subjected to I-R, or neonatal rat cardiomyocytes subjected to hypoxia-re-oxygenation. 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. Over-expression of nucleolin was cytoprotective, whereas nucleolin ablation enhanced both hypoxia- and H₂O₂-induced cardiomyocyte death. Furthermore, transgenic mice with cardiac-specific over-expression 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 heat shock protein 32 (Hsp32), resulting in an increase of Hsp32 mRNA stability, and subsequent up-regulation of Hsp32 expression. The selective Hsp32 inhibitor, zinc protoporphyrin-IX, 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 the regulation of Hsp32, and may be a novel therapeutic target for ischaemic heart diseases.
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Bimei
authors.initials: B
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Chunliu
authors.initials: C
authors.lastname: Lv
authors.forename: Zizhi
authors.initials: Z
authors.lastname: Tu
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019295:Computational Biology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000633:toxicity; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D000097796:Nucleolin
chemical_list: D020413:3' Untranslated Regions; D004791:Enzyme Inhibitors; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D016877:Oxidants; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C496542:Hmox1 protein, mouse; C491523:Hmox1 protein, rat
keywords: Cardioprotection; Hsp32; Ischaemia–reperfusion injury; Nucleolin; mRNA stability