title: Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models.
abstract: Bax and Bak, two pro-apoptotic Bcl-2 family proteins, have been implicated in acute kidney injury following renal ischemia/reperfusion; however, definitive evidence for a role of these genes in the disease process is lacking. Here we first examined two Bax-deficient mouse models and found that only conditional Bax deletion specifically from proximal tubules could ameliorate ischemic acute kidney injury. Global (whole mouse) knockout of Bax enhanced neutrophil infiltration without significant effect on kidney injury. In contrast, global knockout of Bak protected mice from ischemic acute kidney injury with improved renal function. Interestingly, in these models, Bax or Bak knockout attenuated renal tubular cell apoptosis without significantly affecting necrotic tubular damage. Cytochrome c release in ischemic acute kidney injury was also suppressed in conditional Bax- or global Bak-knockout mice. In addition, Bak deficiency prevented mitochondrial fragmentation in ischemic acute kidney injury. Thus, our gene-knockout studies support a critical role of Bax and Bak in tubular cell apoptosis in ischemic acute kidney. Furthermore, necrosis and apoptosis have distinguishable regulatory functions.
authors: Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA. qwei@gru.edu
authors: Qingqing
authors: Q
authors: Wei
authors: Guie
authors: G
authors: Dong
authors: Jian-Kang
authors: JK
authors: Chen
authors: Ganesan
authors: G
authors: Ramesh
authors: Zheng
authors: Z
authors: Dong
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D020556:Neutrophil Infiltration; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c