Janus kinase/signal transducer and activator of transcription inhibitors enhance the protective effect mediated by tanshinone IIA from hypoxic/ischemic injury in cardiac myocytes.

Abstract

Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus‑activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia‑induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic‑ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.

• Authors: Mei-Qi Zhang, Jian-Feng Tu, Huan Chen, Ye Shen, Ling-Xiao Pang, Xiang-Hong Yang, Ren-Hua Sun, Yue-Liang Zheng
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 11 Issue 4 Pg. 3115-21 (Apr 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25502794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abietanes
• Cardiotonic Agents
• Protein Kinase Inhibitors
• STAT Transcription Factors
• tanshinone
• Janus Kinase 2
• Janus Kinases

Topics

• Abietanes (pharmacology)
• Animals
• Apoptosis (drug effects)
• Cardiotonic Agents (pharmacology)
• Cell Survival (drug effects)
• Disease Models, Animal
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Janus Kinases (antagonists & inhibitors, metabolism)
• Male
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Rats
• STAT Transcription Factors (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)