title: Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts.
abstract: OBJECTIVE
  This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts.
  
  
  BACKGROUND
  The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied.
  
  
  METHODS
  Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H(2)O(2)) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis.
  
  
  RESULTS
  The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H(2)O(2) (100 to 800 microM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 microM) and across increasing doses of H(2)O(2) (100 to 800 microM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H(2)O(2), but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH(2)-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione.
  
  
  CONCLUSIONS
  Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.
authors.affiliation: Gerontology Division, Department of Medicine, Beth Israel Deaconess Medical Center and the Division on Aging, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Azhar
authors.forename: K
authors.initials: K
authors.lastname: Nagano
authors.forename: J Y
authors.initials: JY
authors.lastname: Wei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D020929:Mitogen-Activated Protein Kinase Kinases