Role of Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in cardioprotection of exercise preconditioning.

Abstract

OBJECTIVE:

To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the cardioprotective mechanisms of exercise preconditioning (EP).

MATERIALS AND METHODS:

Eighty male Sprague-Dawley (SD) rats were randomized into the Group control, Group EE, Group EP+EE, Group EP+EE+AG, and Group EE+AG. By using 3 days of intermittent treadmill exercise, this study established the EP animal model. Rats were subjected to run to exhaustion on the treadmill at 30 m/min with 0% grade as an exhaustive exercise (EE) protocol. The myocardial injury induced by exhaustive exercise was produced 24 h after EP. JAK2 inhibitor (AG490, 3 mg/kg) was injected before EP. Serum cardiac troponin I (cTnI) levels and hematoxylin basic fuchsine picric acid (HBFP) staining were used to observe the degree of myocardial ischemia. TUNEL, Bcl2, and cleaved caspase-3 levels were used to evaluate the change of myocardial apoptosis. Moreover, the phosphorylations of JAK2 and STAT3 were analyzed as possible mechanisms that might explain the EP-induced cardioprotection.

RESULTS:

EP significantly attenuated the exhaustive exercise-induced myocardial ischemia injury, associated with lower serum cTnI levels, decreased myocardial infarct area, reduced myocardial apoptosis, increased Bcl2 level, decreased cleaved caspase-3 level, and the increased phosphorylations of JAK2 and STAT3. Treatment with AG490 abolished the cardioprotective effects and the enhanced phosphorylations of JAK2 and STAT3 induced by EP.

CONCLUSIONS:

EP plays its cardioprotective role via activating the JAK2/STAT3 signaling pathway, reducing the apoptosis of myocardial cells and alleviating myocardial ischemia injury.

• Authors: X-J Sun, J-R Mao
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 22 Issue 15 Pg. 4975-4986 (08 2018) ISSN: 2284-0729 [Electronic] Italy
• PMID: 30070334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• Troponin I
• Tyrphostins
• alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
• Janus Kinase 2
• Caspase 3

Topics

• Animals
• Apoptosis
• Caspase 3 (metabolism)
• Janus Kinase 2 (metabolism)
• Male
• Myocardial Ischemia (metabolism, pathology)
• Myocardium (metabolism, pathology)
• Phosphorylation (drug effects)
• Physical Conditioning, Animal
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Troponin I (blood)
• Tyrphostins (pharmacology)