Postconditioning inhibits myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway

• Published in: Journal of biomedical science Vol. 18; no. 1; p. 53
• Main Authors: Tian, Yikui, Zhang, Wenjuan, Xia, Dachuan, Modi, Paul, Liang, Degang, Wei, Minxin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02-08-2011; BioMed Central; BMC
• Subjects: Analysis; Androstadienes - pharmacology; Animals; Apoptosis; Apoptosis - physiology; Bcl-2; Blotting, Western; Immunohistochemistry; In Situ Nick-End Labeling; Ischemia; Ischemia/reperfusion injury; Ischemic Postconditioning - methods; JAK2-STAT3 pathway; Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - metabolism; Messenger RNA; Myocardial Reperfusion - methods; Myocardium - cytology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; postconditioning; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; STAT3 Transcription Factor - metabolism; Tyrphostins - pharmacology
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/1423-0127-18-53

Postconditioning (PostC) inhibits myocardial apoptosis after ischemia-reperfusion (I/R) injury. The JAK2-STAT3 pathway has anti-apoptotic effects and plays an essential role in the late protection of preconditioning. Our aim was to investigate the anti-apoptotic effect of PostC after prolonged reperfusion and the role of the JAK2-STAT3 pathway in the anti-apoptotic effect of PostC.
Wistar rats were subjected to 30 minutes ischemia and 2 or 24 hours (h) reperfusion, with or without PostC (three cycles of 10 seconds reperfusion and 10 seconds reocclusion at the onset of reperfusion). Separate groups of rats were treated with a JAK2 inhibitor (AG490) or a PI3K inhibitor (wortmannin) 5 minutes before PostC. Immunohistochemistry was used to analyze Bcl-2 protein levels after reperfusion. mRNA levels of Bcl-2 were detected by qRT-PCR. TTC staining was used to detect myocardial infarction size. Myocardial apoptosis was evaluated by TUNEL staining. Western-blot was used to detect p-STAT3 and p-Akt levels after reperfusion.
There was more myocardial apoptosis at 24 h vs 2 h after reperfusion in all groups. PostC significantly reduced myocardial apoptosis and elevated Bcl-2 levels at both 2 and 24 hours after reperfusion. PostC increased p-STAT3 and p-Akt levels after reperfusion. Administration of AG490 reduced p-STAT3 and p-Akt levels and attenuated the anti-apoptotic effect of PostC. Wortmannin also reduced p-Akt levels and attenuated the anti-apoptotic effect of PostC but had no effect on p-STAT3 levels. AG490 abrogated the up-regulation of Bcl-2 by PostC.
PostC may reduce myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway. As a downstream target of JAK2 signaling, activation of PI3K/Akt pathway may be necessary in the protection of PostC.