title: Calcineurin B subunit acts as a potential agent for preventing cardiac ischemia/reperfusion injury.
abstract: Calcineurin B subunit (CnB) is the regulatory subunit of calcineurin (Cn), a Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase. It has been reported that mice deleting the CnB gene lose nearly all Cn activity and show poor tolerance to cardiac stress; CnB gene expression is downregulated in the hearts of rats that have suffered ischemia/reperfusion (I/R) injury. Therefore, we wonder whether injection of exogenous CnB protein can prevent the rats from suffering I/R injury. In cardiomyocytes, fluorogenic labeling shows that exogenous CnB quickly enters the cell. Pretreatment of cardiomyocytes with CnB reduces apoptosis in response to hypoxia/reoxygenation injury (an in vitro model mimicking ischemia/reperfusion injury), and CsA reverses this effect by inhibiting Cn activity. Furthermore, CnB upregulates Bcl-2 and Bcl-XL expression in the process of hypoxia/reoxygenation injury, which may contribute to protecting cardiomyocytes against apoptosis. In vivo experiments shows that pretreatment with CnB improves cardiac contractile function and reduces the frequency of arrhythmias induced by global I/R injury. These findings reveal a novel function for CnB protein in cardiac stress response and suggest a possible application of CnB in coronary disease therapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Genetic Engineering Medicine and Biotechnology, Beijing Normal University, Beijing, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Guo
authors.forename: Shengquan
authors.initials: S
authors.lastname: Mi
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Yin
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019703:Calcineurin / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000378:metabolism*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002316:Cardiotonic Agents; D021122:Protein Subunits; D019253:Proto-Oncogene Proteins c-bcl-2; D019703:Calcineurin