Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes

Biochem Biophys Res Commun. 2004 Apr 23;317(1):162-8. doi: 10.1016/j.bbrc.2004.03.021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD*
  • Antigens, Neoplasm*
  • Basigin
  • Cell Hypoxia / physiology
  • Cells, Cultured
  • Cyclophilin A / genetics
  • Cyclophilin A / metabolism*
  • Gene Expression
  • Heart Ventricles / metabolism
  • Immunohistochemistry
  • Membrane Glycoproteins / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism*
  • Oxygen / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • bcl-X Protein

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Bcl2l1 protein, rat
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-X Protein
  • Basigin
  • Protein Serine-Threonine Kinases
  • Cyclophilin A
  • Oxygen