Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes
Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes
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DOI：
10.1016/j.bbrc.2004.03.021
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发表时间：
2004-04-23
影响因子：
3.1
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Seko, Y;Fujimura, T;Nagai, R
我们之前报道过缺氧和复氧（缺氧/复氧）会快速激活细胞内信号传导，例如丝裂原激活蛋白激酶（MAPK），包括细胞外信号调节蛋白激酶（ERK）1/2、p38MAPK和应激激活蛋白激酶（SAPK）。为了研究介导心脏对缺氧/复氧反应的体液因素，我们通过二维电泳和质谱分析了来自缺氧/复氧的心肌细胞的条件培养基。我们确定亲环蛋白 A (CyPA) 是心肌细胞响应缺氧/复氧而分泌的蛋白质之一。缺氧/复氧诱导体外心肌细胞上 CyPA 及其细胞表面受体 CD 147 的表达。这也通过体内缺血/再灌注得到证实。重组人 (rh) CyPA 激活培养的心肌细胞中的 ERK1/2、p38MAPK、SAPK 和 Akt。此外，CyPA 显着增加心肌细胞中的 Bcl-2。这些数据强烈表明，CyPA 是响应缺氧/复氧而从心肌细胞中释放出来的，并且可以保护心肌细胞免受氧化应激诱导的细胞凋亡。 (C) 2004 Elsevier Inc. 保留所有权利。
We previously reported that hypoxia followed by reoxygenation (hypoxia/reoxygenation) rapidly activated intracellular signaling such as mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated protein kinase (ERK) 1/2, p38MAPK, and stress-activated protein kinases (SAPKs). To investigate the humoral factors which mediate cardiac response to hypoxia/reoxygenation, we analyzed the conditioned media from cardiac myocytes subjected to hypoxia/reoxygenation by two-dimensional electrophoresis and mass spectrometry. We identified cyclophilin A (CyPA) as one of the proteins secreted from cardiac myocytes in response to hypoxia/reoxygenation. Hypoxia/reoxygenation induced the expression of CyPA and its cell surface receptor CD 147 on cardiac myocytes in vitro. This was also confirmed by ischemia/reperfusion in vivo. Recombinant human (rh) CyPA activated ERK1/2, p38MAPK, SAPKs, and Akt in cultured cardiac myocytes. Furthermore, CyPA significantly increased Bcl-2 in cardiac myocytes. These data strongly suggested that CyPA is released from cardiac myocytes in response to hypoxia/reoxygenation and may protect cardiac myocytes from oxidative stress-induced apoptosis. (C) 2004 Elsevier Inc. All rights reserved.