title: Previous ischemia and reperfusion injury results in resistance of the kidney against subsequent ischemia and reperfusion insult in mice; a role for the Akt signal pathway.
abstract: BACKGROUND
  Kidneys previously exposed to ischemia and reperfusion (I/R), pre-conditioned by I/R, are less susceptible to subsequent I/R injury. Here, we investigated the role for protein kinase B (Akt) survival signaling pathways including anti-apoptosis pathways in the reduced susceptibility of I/R-pre-conditioned kidneys.
  
  
  METHODS
  Mice were exposed to either a single I/R pre-conditioning event (SIRPC, 30 min of bilateral renal ischemia followed by 8 days of reperfusion) or sham-operation (non-SIRPC) and then subjected to either 30 min of bilateral renal ischemia or sham-operation (sham). Some of the mice received intra-peritoneal administrations of wortmannin, which is an inhibitor of phosphatidylinositol-3 kinase, PI3K.
  
  
  RESULTS
  Thirty minutes of bilateral renal ischemia in non-SIRPC mice induced a dramatic increase in plasma creatinine (PCr) levels, but this was not observed in the SIRPC mouse. Consistent with the PCr results, tubular damage and apoptotic tubular cell death were more severe in the non-SIRPC mouse kidney than in the SIRPC mice. SIRPC increased the levels of phosphorylated-Akt and -Bad expression as well as the ratio of Bcl-2 to Bax expression in the kidney. I/R resulted in greater increases of phosphorylated-Akt and -Bad, Bcl-xL and Bcl-2, but a lower level of increase of Bax, in the SIRPC mouse kidneys than those in the non-SIRPC-mouse kidneys. Treatment with wortmannin during the SIRPC period inhibited SIRPC-induced increase in phosphorylated-Akt and -Bad expressions and eliminated tolerance of SIRPC mice kidneys to I/R insult.
  
  
  CONCLUSIONS
  Ischemic pre-conditioning confers renal resistance to I/R-induced apoptosis via activation of the Akt signal pathway.
authors.affiliation: Department of Anatomy, Kyungpook National University School of Medicine, Dongindong, Junggu, Daegu, Korea.
authors.forename: Hee-Seong
authors.initials: HS
authors.lastname: Jang
authors.forename: Jinu
authors.initials: J
authors.lastname: Kim
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kim
authors.forename: Min Hyun
authors.initials: MH
authors.lastname: Cho
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D007511:Ischemia / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000730:Androstadienes; C494820:Bad protein, mouse; C494812:Bcl2l1 protein, mouse; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin