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The ERK1/2 signaling pathway is involved in sulfur dioxide preconditioning-induced protection against cardiac dysfunction in isolated perfused rat heart subjected to myocardial ischemia/reperfusion.

Abstract
Ischemia/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO2) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway mediated protection against cardiac dysfunction after SO2 preconditioning in isolated rat hearts subjected to ischemia/reperfusion (I/R). Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 μmol/L SO2 group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) + 5 μmol/L SO2 (PD98059 + S5) group, PD98059 group, I/R group, 5 μmol/L SO2 + I/R (S5 + I/R) group and PD98059 + 5 μmol/L SO2 + I/R (PD98059 + S5 + I/R) group. Cardiac function and myocardial phosphorylated ERK1/2 protein were measured. We found that I/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1/2 protein. SO2 preconditioning markedly suppressed phosphorylated ERK1/2 protein and improved cardiac function in isolated rat heart with I/R (p < 0.05). However, pre-treatment with PD98059 could prevent the above effects of SO2 preconditioning. In conclusion, SO2 preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I/R via suppression of the over-activation of the ERK1/2 signaling pathway.
AuthorsPan Huang, Yan Sun, Jinyan Yang, Siyao Chen, Angie Dong Liu, Lukas Holmberg, Xiaomei Huang, Chaoshu Tang, Junbao Du, Hongfang Jin
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 11 Pg. 22190-201 (Nov 08 2013) ISSN: 1422-0067 [Electronic] Switzerland
PMID24217229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cardiotonic Agents
  • Flavonoids
  • Sulfur Dioxide
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Topics
  • Animals
  • Cardiotonic Agents (administration & dosage)
  • Flavonoids (administration & dosage)
  • Heart Failure (drug therapy, metabolism, pathology)
  • Humans
  • Ischemic Preconditioning
  • MAP Kinase Signaling System (drug effects)
  • Male
  • Myocardium (metabolism)
  • Phosphorylation (drug effects)
  • Rats
  • Reperfusion Injury (drug therapy, pathology)
  • Sulfur Dioxide (administration & dosage)

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