Metallothionein mediates cardioprotection of isoliquiritigenin against ischemia-reperfusion through JAK2/STAT3 activation

Authors: AN, Wei1; YANG, Jing; AO, Ying1

Source: Acta Pharmacologica Sinica, Volume 27, Number 11, November 2006 , pp. 1431-1437(7)

Publisher: Blackwell Publishing

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Abstract:

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.

Keywords: isoliquiritigenin; myocardial ischemia-reperfusion; metallothionein; janus kinase; STAT3 transcription factors

Document Type: Research article

DOI: 10.1111/j.1745-7254.2006.00419.x

Affiliations: 1: Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071, China

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