title: Role of p53-dependent activation of caspases in chronic obstructive uropathy: evidence from p53 null mutant mice.
abstract: Chronic obstructive uropathy (COU) created by unilateral ureteric ligation is associated with increased renal cell apoptosis and p53 expression. Genetically engineered mice were used to examine the role of p53 in renal cell apoptosis in COU and the involved molecular pathways. Obstructed kidneys in p53+/+, p53+/-, and p53-/- mice were examined at days 4, 7, 15, 20, and 30 for apoptosis, and mRNA were examined for p53, members of the bcl-2 family, the death receptor family, and the common effectors of apoptosis. Obstructed kidneys in p53+/- and p53-/- mice exhibited equal attenuation of tubular and interstitial cell apoptosis (70 and 50%, respectively), compared with p53+/+ mice. However, p53 gene deficiency did not confer complete protection from apoptosis. Obstructed kidneys from p53-/- mice did not express p53 mRNA, whereas those from p53+/- and p53+/+ mice displayed mild and marked increase in their expression, respectively. Obstructed kidneys in p53+/+, p53+/-, and p53-/- mice displayed upregulation of mRNA for members of the bcl-2 family and most of the death receptor family, except for a lower level of tumor necrosis factor receptor-1, TRAIL, and FAP in p53+/+ mice. Obstructed kidneys in p53-/- and p53+/- mice showed virtual absence of caspase 11 and marked attenuation of caspases 1 and 12, contrasted with their strong expression in p53+/+ kidneys. These data suggest that apoptosis in obstructed kidneys involves p53-dependent as well as p53-independent pathways. The p53-dependent pathway may involve activation of caspases 1, 11, and 12, whereas the p53-independent pathway may involve activation of members of the bcl-2 and death receptor families.
authors.affiliation: Renal Pathology Laboratory, Department of Pathology The Methodist Hospital Houston, Texas.
authors.forename: Yeong-Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Medicine, The Methodist Hospital Houston, Texas.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mendoza
authors.affiliation: Renal Pathology Laboratory, Department of Pathology The Methodist Hospital Houston, Texas.
authors.forename: Suk-Joo
authors.initials: SJ
authors.lastname: Rha
authors.affiliation: Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.affiliation: Renal Pathology Laboratory, Department of Pathology The Methodist Hospital Houston, Texas.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Baranowska-Daca
authors.affiliation: Renal Pathology Laboratory, Department of Pathology The Methodist Hospital Houston, Texas.
authors.forename: Vinh
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, The Methodist Hospital Houston, Texas.
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
authors.forename: George
authors.initials: G
authors.lastname: Nassar
authors.affiliation: Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
authors.forename: Wadi N
authors.initials: WN
authors.lastname: Suki
authors.affiliation: Renal Pathology Laboratory, Department of Pathology The Methodist Hospital Houston, Texas.|Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.
authors.forename: Luan D
authors.initials: LD
authors.lastname: Truong
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D019254:Genes, bcl-2; D016158:Genes, p53; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D020169:Caspases