Remote ischemic postconditioning protects against renal ischemia/reperfusion injury by activation of T-LAK-cell-originated protein kinase (TOPK)/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation
Remote ischemic postconditioning protects against renal ischemia/reperfusion injury by activation of T-LAK-cell-originated protein kinase (TOPK)/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation
复制标题
远程缺血后处理通过激活 T-LAK 细胞源性蛋白激酶 (TOPK)/PTEN/Akt 信号通路介导的抗氧化和抗炎作用来防止肾缺血/再灌注损伤
DOI：
10.1016/j.intimp.2016.06.020
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发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Yuan, Shiying
中科院分区：
文献类型：
--
作者：
Gao, Sumin;Zhu, Yi;Yuan, Shiying
Background: Recent clinical and animal studies suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection or neuroprotection. However, the effect and mechanism of RlPostC against renal ischemia/reperfusion injury (IRI) are poorly understood. T-LAK-cell-originated protein kinase (TOPIC) is crucial for the proliferation and migration of tumor cells. However, the function of TOPIC and the molecular mechanism underlying renal protection remain unknown. Therefore, this study aimed to evaluate the role of TOPK in renoprotection induced by RlPostC.Materials and Methods: The renal IRI model was induced by left renal pedicle clamping for 45 min followed by 24 h reperfusion and right nephrectomy. All mice were intraperitoneally injected with vehicle, TOPIC inhibitor HI-TOPK-032 or Akt inhibitor LY294002. After 24 h reperfusion, renal histology, function, and inflammatory cytokines and oxidative stress were assessed. The proteins were measured by Western blotting.Results: The results showed that RIPostC significantly protected the kidneys against IRI. The protective effects were accompanied by the attenuation of renal dysfunction, tubular damage, inflammation and oxidative stress. In addition, RIPostC increased the phosphorylation of TOPIC, PI EN, Akt, GSK3 beta and the nuclear translocation of Nrf2 and decreased the nuclear translocation of NF-kappa B. However, all of the above renoprotective effects of RIPostC were eliminated either by the inhibition of TOPIC or Akt with HI-TOPIC-032 or LY294002.Conclusions: The current data reveal that RIPostC protects against renal IRI via activation of TOPK/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation. (C) 2016 Elsevier B.V. All rights reserved.
