title: Renoprotective effect of erythropoietin in ischemia/reperfusion injury: possible roles of the Akt/endothelial nitric oxide synthase-dependent pathway.
abstract: OBJECTIVE
  It has been reported that erythropoietin protects the kidneys from ischemia/reperfusion injury. In the present study, we examined the role of Akt and endothelial nitric oxide synthase in the protective effect of erythropoietin on ischemia/reperfusion injury of the kidney.
  
  
  METHODS
  Erythropoietin was injected in the peritoneal space of ICR mice after ischemia/reperfusion injury and its effect was assessed by measuring blood urea nitrogen and creatinine, and by histological analysis. Phosphorylation of Akt and endothelial nitric oxide synthase was examined by western blot analysis. Endothelial nitric oxide synthase gene null mice were also used to examine the role of endothelial nitric oxide synthase in the renoprotective effect of erythropoietin.
  
  
  RESULTS
  Erythropoietin administration significantly inhibited the increase in blood urea nitrogen and creatinine after ischemia/reperfusion injury compared with control mice. Accordingly, erythropoietin administration significantly ameliorated the histological damages, including apoptotic cell death. Erythropoietin significantly stimulated phosphorylation of Akt and endothelial nitric oxide synthase in the kidneys. When endothelial nitric oxide synthase gene null mice were subjected to ischemia/reperfusion injury, erythropoietin did not significantly suppress the increase in blood urea nitrogen or creatinine.
  
  
  CONCLUSIONS
  Erythropoietin seems to activate the Akt/endothelial nitric oxide synthase-dependent pathway in the kidneys. This pathway might be implicated in the renoprotective effect of erythropoietin in the ischemia/reperfusion injury model.
authors: Department of Internal MedicineUniversity of Tokyo, Tokyo, Japan.
authors: Shigeyoshi
authors: S
authors: Oba
authors: Etsu
authors: E
authors: Suzuki
authors: Hiroaki
authors: H
authors: Nishimatsu
authors: Shintaro
authors: S
authors: Kumano
authors: Chihiro
authors: C
authors: Hosoda
authors: Yukio
authors: Y
authors: Homma
authors: Yasunobu
authors: Y
authors: Hirata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction
chemical_list: D004921:Erythropoietin; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt