In:
Nephron Experimental Nephrology, S. Karger AG, Vol. 110, No. 3 ( 2008-10-27), p. e82-e90
Abstract:
〈 i 〉 Background/Aims: 〈 /i 〉 The von Hippel-Lindau (VHL) protein functions as an E3 ubiquitin ligase, controlling the stability of hypoxia-inducible factor (HIF). Preinduction of HIF-1α 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 〈 i 〉 VHL 〈 /i 〉 gene might play a role in the response of mice to ischemic renal injury. 〈 i 〉 Methods: 〈 /i 〉 We generated tamoxifen-inducible conditional 〈 i 〉 VHL 〈 /i 〉 knockout ( 〈 i 〉 VHL-KO) 〈 /i 〉 mice to inactivate the 〈 i 〉 VHL 〈 /i 〉 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. 〈 i 〉 Results: 〈 /i 〉 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 〈 i 〉 VHL-KO 〈 /i 〉 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 〈 i 〉 VHL-KO 〈 /i 〉 mice (p 〈 0.05). 〈 i 〉 Conclusion: 〈 /i 〉 We suggest that the acute inactivation of the 〈 i 〉 VHL 〈 /i 〉 gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse.
Type of Medium:
Online Resource
ISSN:
1660-2129
Language:
English
Publisher:
S. Karger AG
Publication Date:
2008
detail.hit.zdb_id:
2098337-2
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