Edaravone attenuates myocyte apoptosis through the JAK2/STAT3 pathway in acute myocardial infarction.

Abstract

Basic and clinical studies have demonstrated that the free radical scavenger edaravone has cytoprotective effects on acute myocardial infarction (AMI) but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the JAK2/STAT3 signaling pathway. AMI in rats was established by left anterior descending coronary artery ligation. Two hours after AMI model established rats were treated with edaravone, edaravone plus AG490, physiological saline, respectively. We detected antioxidant effects by reduced glutathione (GSH), glutathione S-transferase (GST), and Glutathione Peroxidase (GSHPx) Activity. The expressions of t-JAK2, p-JAK2, t-STAT3, p-STAT3 and cleaved caspase-3 were examined by western blot. The mRNA levels for Bcl-2, Bax, Fas, and FasL were measured by RT-PCR and apoptosis was assessed by TUNEL. Edaravone significantly improved hemodynamics after AMI (p < 0.05) and reduced the total infarct volumes (p < 0.05). Compared with Sham rats, the mRNA of Bax, Fas, and FasL increased in different degrees in the AMI group, however, the mRNA of Bcl-2 and the ratio of Bcl-2/Bax decreased, especially the myocardial apoptosis index significantly increased in AMI hearts (all p < 0.05). After treatment with edaravone, the mRNA levels of Bcl-2 and the ratio of Bcl-2/Bax significantly upregulated whereas Bax, Fas, FasL apparently decreased, and the protein expressions of p-JAK2 and p-STAT3 dramatically increased (p < 0.05). In addition, cotreatment with JAK2 inhibitor AG490 abolished the effects of edaravone. We conclude that edaravone attenuated myocardial apoptosis induced by AMI via JAK2/STAT3 signaling pathway.

• Authors: Hui Chen, Yongjun Chen, Xin Wang, Jing Yang, Congxin Huang
• Journal: Free radical research (Free Radic Res) Vol. 54 Issue 5 Pg. 351-359 (May 2020) ISSN: 1029-2470 [Electronic] England
• PMID: 32543312 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• STAT3 Transcription Factor
• Stat3 protein, rat
• Jak2 protein, rat
• Janus Kinase 2
• Edaravone

Topics

• Acute Disease
• Animals
• Apoptosis (drug effects)
• Edaravone (chemistry, pharmacology)
• Janus Kinase 2 (genetics, metabolism)
• Male
• Muscle Cells (drug effects)
• Myocardial Infarction (drug therapy, metabolism)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)