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Acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in the mouse kidney.

Author	Mitsuko Iguchi, Yoshihiko Kakinuma, Atsushi Kurabayashi, Takayuki Sato, Taro Shuin, Seung-Beom Hong, Laura S Schmidt, Mutsuo Furihata
Citation Information	Nephron. Experimental nephrology, 110:e82-90 (2008)
Keywords	Animals, Ischemic Preconditioning, Kidney, Mice, Reperfusion Injury, Von Hippel-Lindau Tumor Suppressor Protein
Related Products	S7100
Pub Med ID	18957870

BACKGROUND/AIMS: 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). CONCLUSION: We suggest that the acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse.