Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes |
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Authors: | Seko Yoshinori Fujimura Tsutomu Taka Hikari Mineki Reiko Murayama Kimie Nagai Ryozo |
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Affiliation: | Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan. sekoyosh-tky@umin.ac.jp |
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Abstract: | 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 CD147 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. |
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Keywords: | Apoptosis Autocrine Cardiac myocyte CD147 Cyclophilin Hypoxia Ischemia Reoxygenation Reperfusion Signal transduction |
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