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Cyclophilin A is a secreted growth factor induced by oxidative stress
- Source :
- Circulation research. 87(9)
- Publication Year :
- 2000
-
Abstract
- Abstract —Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis, hypertension, and restenosis, in part by promoting vascular smooth muscle cell (VSMC) growth. Many VSMC growth factors are secreted by VSMC and act in an autocrine manner. Here we demonstrate that cyclophilin A (CyPA), a member of the immunophilin family, is secreted by VSMCs in response to oxidative stress and mediates extracellular signal–regulated kinase (ERK1/2) activation and VSMC growth by reactive oxygen species. Human recombinant CyPA can mimic the effects of secreted CyPA to stimulate ERK1/2 and cell growth. The peptidyl-prolyl isomerase activity is required for ERK1/2 activation by CyPA. In vivo, CyPA expression and secretion are increased by oxidative stress and vascular injury. These findings are the first to identify CyPA as a secreted redox-sensitive mediator, establish CyPA as a VSMC growth factor, and suggest an important role for CyPA and enzymes with peptidyl-prolyl isomerase activity in the pathogenesis of vascular diseases.
- Subjects :
- Male
Nitroprusside
Isomerase activity
Physiology
medicine.medical_treatment
Cypa
Apoptosis
Biology
Transfection
Muscle, Smooth, Vascular
Rats, Sprague-Dawley
Cyclophilin A
Onium Compounds
medicine
Animals
NADH, NADPH Oxidoreductases
Vascular Diseases
Enzyme Inhibitors
Autocrine signalling
Cyclophilin
Peptidylprolyl isomerase
Mitogen-Activated Protein Kinase 3
Growth factor
NADPH Oxidases
Free Radical Scavengers
Peptidylprolyl Isomerase
biology.organism_classification
Recombinant Proteins
Cell biology
Rats
Enzyme Activation
Oxidative Stress
Biochemistry
Cis-trans-Isomerases
cardiovascular system
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Aminoquinolines
Mitogen-Activated Protein Kinases
Cardiology and Cardiovascular Medicine
Carotid Artery Injuries
Reactive Oxygen Species
Cell Division
Subjects
Details
- ISSN :
- 15244571
- Volume :
- 87
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Circulation research
- Accession number :
- edsair.doi.dedup.....5becdc50dede0e92f05d8d77d3ece803