Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes.
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.
Seko
Yoshinori
Y
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan. sekoyosh-tky@umin.ac.jp
Fujimura
Tsutomu
T
Taka
Hikari
H
Mineki
Reiko
R
Murayama
Kimie
K
Nagai
Ryozo
R
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C494813:Bcl2l1 protein, rat; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D051926:Basigin; D017346:Protein Serine-Threonine Kinases; D021984:Cyclophilin A; D010100:Oxygen