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Title Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia / Reperfusion Injury in Mice : Activation of JAK / STAT 3-Mediated Nrf 2-Antioxidant Signalling
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gaoa, Sumin Zhanb, Leyun Shia, Zhengchao Yanga Ruili Lic, Haobo Xiac, Zhengyuan Yuand, Shiying Wua, Qing-Ping Wanga, Tingting Yaoa, Shanglong |
| Copyright Year | 2017 |
| Abstract | Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. Results: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative Dr Tingting Wang and Prof Shanglong Yao Department of Anaesthesiology, Institute of Anaesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, (China) E-Mail wangtt201307@163.com/ysltian@163.com S. Gao and L. Zhan contribute equally to this work D ow nl oa de d by : 14 7. 8. 23 0. 12 8 12 /2 7/ 20 17 9 :4 5: 52 A M Cell Physiol Biochem 2017;43:1140-1151 DOI: 10.1159/000481755 Published online: October 05, 2017 1141 Cellular Physiology and Biochemistry © 2017 The Author(s). Published by S. Karger AG, Basel www.karger.com/cpb Gao et al.: Nrf2-Antioxidant Signalling in Remote Limb Ischaemic Postconditioning Cardioprotection stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). Conclusion: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/ STAT3-mediated Nrf2-antioxidant signalling. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://hub.hku.hk/bitstream/10722/250246/1/content.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
