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

International Journal of Molecular Sciences

Pan Huang²  Yan Sun²  Jinyan Yang²  Siyao Chen²  Angie Dong Liu¹  Lukas Holmberg¹  Xiaomei Huang²  Chaoshu Tang³  Junbao Du² 

[1] Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden; E-Mails:;Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China; E-Mails:;Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China; E-Mail:

关键词: myocardial ischemia/reperfusion injury;    sulfur dioxide;    preconditioning;    mitogen activated protein kinase;   

DOI  :  10.3390/ijms141122190

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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