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.
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.
Department of Pediatrics, Peking University First Hospital, Xi-An Men Str. No. 1, West District, Beijing 100034, China. jinhongfang51@126.com.
Pan
P
Huang
Yan
Y
Sun
Jinyan
J
Yang
Siyao
S
Chen
Angie Dong
AD
Liu
Lukas
L
Holmberg
Xiaomei
X
Huang
Chaoshu
C
Tang
Junbao
J
Du
Hongfang
H
Jin
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D005419:Flavonoids / Q000008:administration & dosage; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019194:Ischemic Preconditioning; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013458:Sulfur Dioxide / Q000008:administration & dosage*
D002316:Cardiotonic Agents; D005419:Flavonoids; D013458:Sulfur Dioxide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one