title: 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.
abstract: 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 RIPostC against renal ischemia/reperfusion injury (IRI) are poorly understood. T-LAK-cell-originated protein kinase (TOPK) is crucial for the proliferation and migration of tumor cells. However, the function of TOPK and the molecular mechanism underlying renal protection remain unknown. Therefore, this study aimed to evaluate the role of TOPK in renoprotection induced by RIPostC.
  
  
  METHODS
  The renal IRI model was induced by left renal pedicle clamping for 45min followed by 24h reperfusion and right nephrectomy. All mice were intraperitoneally injected with vehicle, TOPK inhibitor HI-TOPK-032 or Akt inhibitor LY294002. After 24h 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 TOPK, PTEN, Akt, GSK3β and the nuclear translocation of Nrf2 and decreased the nuclear translocation of NF-κB. However, all of the above renoprotective effects of RIPostC were eliminated either by the inhibition of TOPK or Akt with HI-TOPK-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.
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Sumin
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wangtt201307@163.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yuan_shiying@163.com.
authors.forename: Shiying
authors.initials: S
authors.lastname: Yuan
mesh_terms: D000818:Animals; D007249:Inflammation / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; C000616811:TOPK protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Akt; NF-κB; Nrf2; PTEN; Remote ischemic postconditioning; TOPK