title: Mechanical deformation induced apoptosis in human proximal renal tubular epithelial cells is caspase dependent.
abstract: OBJECTIVE
  Ureteral obstruction (UO) results in apoptosis of renal tubular epithelial cells. We postulated that mechanical deformation and inflammation contribute to the cellular loss that occurs as a result of UO and it is mediated through altered heat shock protein 70 (HSP-70) expression and the caspase cascade.
  
  
  METHODS
  Human HK-2 renal tubular cells were subjected to mechanical stretch. Cell viability and apoptosis were assessed by flow cytometry; HSP-70 and caspase 3 protein expression by Western blotting, and caspase 3 activity by fluorescence substrates.
  
  
  RESULTS
  Mechanical stretch caused direct apoptosis induction and it also primed for tumor necrosis factor-alpha induced apoptosis, which was caspase 3 dependent. Although HSP-70 protein expression was increased during mechanical stretch, the protective effects of HSP-70 were only seen after further induction by heat shocking.
  
  
  CONCLUSIONS
  Altering HSP-70 expression and manipulating the caspase cell death proteases represent a novel pathway to protect against renal tubular cell apoptosis and the potential for progression to renal failure in UO.
authors.affiliation: Department of Surgerr Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research and Dublin Molecular Medical Centre, University College Dublin, Ireland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Power
authors.forename: Belinda T
authors.initials: BT
authors.lastname: Doyle
authors.forename: Debra
authors.initials: D
authors.lastname: Higgins
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Brady
authors.forename: John M
authors.initials: JM
authors.lastname: Fitzpatrick
authors.forename: R William G
authors.initials: RW
authors.lastname: Watson
mesh_terms: D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D013314:Stress, Mechanical; D014517:Ureteral Obstruction / Q000473:pathology
chemical_list: D061945:Caspase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D020169:Caspases