title: Eicosapentanoic acid inhibits hypoxia-reoxygenation-induced injury by attenuating upregulation of MMP-1 in adult rat myocytes.
abstract: BACKGROUND
  Myocardial hypoxia-reoxygenation (H-R) is associated with upregulation of metalloproteinases (MMPs). Upregulation of MMPs is associated with cell injury. Previous studies have shown that fish oil can protect myocardium from injury induced by H-R. This study was designed to examine the effect of eicosapentanoic acid (EPA), one of the major components in fish oil, on the modulation of MMP-1 expression in response to H-R in cultured adult rat myocytes.
  
  
  RESULTS
  Myocytes isolated from adult Sprague-Dawley rat hearts were cultured with or without EPA or arachidonic acid (AA) (10 and 50 microM) and exposed to 24 h of hypoxia followed by 3 h of reoxygenation (H-R). H-R resulted in myocyte injury (measured on LDH release), increase in p38MAPK phosphorylation (Western analysis), augmentation of lipid peroxidation, and upregulation of MMP-1 activity (zymography) and expression (RT-PCR and Western analysis) (all P<0.01 vs. control, n=5). Pretreatment of myocytes with EPA, but not AA, resulted in a reduction in LDH release, and attenuation of p38MAPK phosphorylation and MMP-1 activity and expression in response to H-R (all P<0.05 vs. H-R alone). Pretreatment of myocytes with EPA also reduced lipid peroxidation in myocytes exposed to H-R (P<0.05 vs. H-R alone). A high concentration of EPA (50 microM) was more potent than the lower concentration of EPA (10 microM).
  
  
  CONCLUSIONS
  These observations suggest that EPA attenuates an increase in MMP-1 following H-R, which may be a basis of protection of myocytes from the adverse effects of H-R. p38MAPK phosphorylation may be an important signaling event in this process.
authors.affiliation: Department of Medicine, University of Arkansas for Medical Science and Central Arkansas Veterans Health Care System, Little Rock, AR 72205-7199, USA.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Chen
authors.forename: Dayuan
authors.initials: D
authors.lastname: Li
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Roberts
authors.forename: Tom
authors.initials: T
authors.lastname: Saldeen
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000627:therapeutic use*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D012333:RNA, Messenger; D008315:Malondialdehyde; D015118:Eicosapentaenoic Acid; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1