Open AccessMetallothionein mediates cardioprotection of isoliquiritigenin against ischemia‐reperfusion through JAK2/STAT3 activation
Author(s) -
AN Wei,
YANG Jing,
AO Ying
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00419.x
Subject(s) - isoliquiritigenin , cardioprotection , janus kinase , janus kinase 2 , stat , kinase , lactate dehydrogenase , jak stat signaling pathway , mapk/erk pathway , stat3 , signal transduction , phosphorylation , protein kinase b , endocrinology , medicine , chemistry , pharmacology , ischemia , biochemistry , enzyme , receptor tyrosine kinase
Aim: To examine whether isoliquiritigenin (ISL) can attenuate myocardial ischemia‐reperfusion (MI/R) injury in rats by inducing metallothionein (MT) through activation of janus kinase 2 (JAK 2)/signal transducers and activators of transcription 3 (STAT 3) pathway. Methods: The experimental model of MI/R in rats was generated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX‐2, and iNOS were measured by RT‐PCR. The protein expressions of MT, JAK/STAT, extracellular signal‐regulated kinase (ERK), and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 (1.0 mg/kg, iv, 1 h before ischemia). Results: Pretreatment with ISL markedly decreased the severity of reperfusion‐induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphoryla‐tion was accompanied by increased synthesis of MT but not of COX‐2 or iNOS in ISL‐treated groups. AG490 can significantly weaken ISL‐induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation. Conclusion: ISL protected MI/R injury through activation of JAK 2/STAT 3 signal transduction pathway, which might be involved in mediating the upregulation of MT expression.