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.
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An, W., Yang, J. & Ao, Y. Metallothionein mediates cardioprotection of isoliquiritigenin against ischemia-reperfusion through JAK2/STAT3 activation. Acta Pharmacol Sin 27, 1431–1437 (2006). https://doi.org/10.1111/j.1745-7254.2006.00419.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00419.x
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