Impact of brief oxidant stress on primary adult cardiac fibroblasts.
Reperfusion of ischemic myocardium (I/R) is associated with local release of a brief pulse of reactive oxygen species. The purpose of this study was to determine the effects of brief H2O2 stimulation on primary adult cardiac fibroblast phenotype. We demonstrate that brief H2O2 exposure results in transient phosphorylations of p38 and ERK which peaked by 15 min. Proliferation was minimally affected by either H2O2 or MAPK inhibition. Pretreatment with SB203580 or U0126 revealed that p38 enhances or maintains migration rates while ERK retarded migration. Peroxide exposure increased necrosis from 4% at baseline to >12% while reducing apoptosis by 3.5-fold. p38 inhibition resulted in increased necrosis and apoptosis while ERK inhibition had minimal effects. In conclusion, primary adult cardiac fibroblasts exposed to brief H2O2 exhibit an altered phenotype characterized by reduced migration and apoptosis and increased necrosis resulting, in part, from the differential effects of p38 and ERK signaling.
Janey Briscoe Center of Excellence in Cardiovascular Disease, Department of Medicine, Division of Cardiology, University of Texas, Health Science Center at San Antonio, San Antonio, TX 78284, USA. colstonj@uthscsa.edu
James T
JT
Colston
Sam D
SD
de la Rosa
Gregory L
GL
Freeman
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D011921:Rats, Inbred WKY
D016877:Oxidants; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases