Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Genetic Engineering Medicine and Biotechnology, Beijing Normal University, Beijing, China.
Mol Cell Biochem. 2012 Nov;370(1-2):163-71. doi: 10.1007/s11010-012-1407-7. Epub 2012 Aug 28.
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.
钙调神经磷酸酶 B 亚基（CnB）是钙调神经磷酸酶（Cn）的调节亚基，Cn 是一种依赖 Ca2+/钙调蛋白的丝氨酸/苏氨酸蛋白磷酸酶。有报道称，缺失 CnB 基因的小鼠几乎失去了所有的 Cn 活性，对心脏应激的耐受性较差；在经历缺血/再灌注（I/R）损伤的大鼠心脏中，CnB 基因表达下调。因此，我们想知道注射外源性 CnB 蛋白是否可以防止大鼠遭受 I/R 损伤。在心肌细胞中，荧光标记显示外源性 CnB 迅速进入细胞。用 CnB 预处理心肌细胞可减少缺氧/复氧损伤引起的细胞凋亡（体外模拟缺血/再灌注损伤的模型），而 CsA 通过抑制 Cn 活性逆转这种作用。此外，CnB 在缺氧/复氧损伤过程中上调 Bcl-2 和 Bcl-XL 的表达，这可能有助于保护心肌细胞免受细胞凋亡。体内实验表明，CnB 预处理可改善心脏收缩功能，减少整体 I/R 损伤引起的心律失常频率。这些发现揭示了 CnB 蛋白在心脏应激反应中的新功能，并提示 CnB 可能在冠心病治疗中有应用前景。
