The effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the JAK2/STAT3 signaling pathway.

Abstract

In this study, we evaluated the effect of curcumin (Cur) post-treatment on isolated perfused rat hearts that had been subjected to a protocol of ischemia and reperfusion injury. We also examined whether the Janus kinase 2 and signal transducer and activator 3 of transcription (JAK2/STAT3) signaling pathway plays a role in the cardioprotective effects of Cur post-treatment. Isolated perfused rat hearts were subjected to 60 min of ischemia, followed by 60 min of reperfusion. The hearts were exposed to 1-μM Cur during the first 10 min of reperfusion in the absence or presence of the JAK kinase-specific inhibitor AG490 (AG, 1 μM). The Cur treatment conferred a cardioprotective effect, and the treated hearts demonstrated an improved post-ischemic cardiac functional recovery, a decreased myocardial infarct size and decreased lactate dehydrogenase release in the coronary flow, a reduced number of apoptotic cardiomyocytes, up-regulation of the anti-apoptotic protein Bcl2 and down-regulation of the pro-apoptotic protein Caspase3. AG blocked the Cur-mediated cardioprotection by inhibiting the JAK2/STAT3 signaling pathway, as reflected by the abrogation of the Cur-induced up-regulation of Bcl2 and down-regulation of Caspase3. The results suggest that Cur post-treatment can attenuate IR injury through the activation of the JAK2/STAT3 signaling pathway, which transmits a survival signal to the myocardium.

• Authors: Weixun Duan, Yang Yang, Juanjuan Yan, Shiqiang Yu, Jincheng Liu, Jingjun Zhou, Jianying Zhang, Zhenxiao Jin, Dinghua Yi
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 107 Issue 3 Pg. 263 (May 2012) ISSN: 1435-1803 [Electronic] Germany
• PMID: 22466958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• Stat3 protein, rat
• Tyrphostins
• alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
• L-Lactate Dehydrogenase
• Jak2 protein, rat
• Janus Kinase 2
• Casp3 protein, rat
• Caspase 3
• Curcumin

Topics

• Animals
• Apoptosis (drug effects)
• Cardiotonic Agents (pharmacology)
• Caspase 3 (metabolism)
• Curcumin (pharmacology)
• In Vitro Techniques
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Infarction (enzymology, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (enzymology, pathology, physiopathology, prevention & control)
• Myocardium (enzymology, pathology)
• Perfusion
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Tyrphostins (pharmacology)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)