title: Acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in the mouse kidney.
abstract: OBJECTIVE
  The von Hippel-Lindau (VHL) protein functions as an E3 ubiquitin ligase, controlling the stability of hypoxia-inducible factor (HIF). Preinduction of HIF-1alpha before pathological insult activates a self-defense mechanism and suppresses further aggravation of organ or cellular injury by ischemia. We investigated whether acute inactivation of the VHL gene might play a role in the response of mice to ischemic renal injury.
  
  
  METHODS
  We generated tamoxifen-inducible conditional VHL knockout (VHL-KO) mice to inactivate the VHL gene in an acute manner during renal ischemia-reperfusion injury (IRI) induced by bilateral clamping of kidney arteries. Renal IRI is characterized by renal dysfunction and tubular damage.
  
  
  RESULTS
  After the procedure of IRI, blood urea nitrogen (BUN) and creatinine (CRN) levels in control mice were significantly higher (BUN, 138.10 +/- 13.03 mg/dl; CRN, 0.72 +/- 0.16 mg/dl) than in VHL-KO mice (BUN, 52.12 +/- 6.61 mg/dl; CRN, 0.24 +/- 0.04 mg/dl; BUN: p < 0.05; CRN: p < 0.05). Histologically, tubular injury scores were higher in control mice than in VHL-KO mice (p < 0.05).
  
  
  CONCLUSIONS
  We suggest that the acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse.
authors.affiliation: Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Iguchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurabayashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Seung-Beom
authors.initials: SB
authors.lastname: Hong
authors.forename: Laura S
authors.initials: LS
authors.lastname: Schmidt
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
mesh_terms: D000818:Animals; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D015427:Reperfusion Injury / Q000517:prevention & control; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C494469:VHL protein, mouse