title: Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice.
abstract: Tubular cell apoptosis is involved in ischemic renal failure, but the underlying mechanism is unclear. Bid, a proapoptotic Bcl-2 family protein, may regulate the intrinsic as well as the extrinsic pathway of apoptosis. In vivo, Bid is most abundantly expressed in the kidneys. However, the role played by Bid in renal pathophysiology is unknown. Our recent work demonstrated Bid activation during renal ischemia-reperfusion. The current study has determined the role of Bid in ischemic renal injury and renal failure using Bid-deficient mice. In wild-type C57BL/6 mice, Bid was proteolytically processed into active forms during renal ischemia-reperfusion, which subsequently targeted mitochondria. This was accompanied by the development of tissue damage and severe renal failure, showing serum creatinine of 3.0 mg/dl after 48 h of reperfusion. The same ischemic insult induced acute renal failure in Bid-deficient mice, which was nonetheless less severe than the wild-type, showing 1.3 mg/dl serum creatinine. In addition, Bid deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3 activation during 48 h of reperfusion. Compared with wild-type, animal death following renal ischemia was delayed in Bid-deficient mice. Collectively, the results suggest a role for Bid in ischemic renal injury and renal failure.
authors.affiliation: Dept. of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wei
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yin
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012079:Renal Circulation; D051437:Renal Insufficiency / Q000378:metabolism* / Q000401:mortality; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein