Mechanical deformation induced apoptosis in human proximal renal tubular epithelial cells is caspase dependent

J Urol. 2004 Jan;171(1):457-61. doi: 10.1097/01.ju.0000091106.61065.e3.

Abstract

Purpose: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase Inhibitors
  • Caspases / physiology*
  • Cells, Cultured
  • Epithelial Cells
  • HSP70 Heat-Shock Proteins / physiology*
  • Humans
  • Kidney Tubules, Proximal / cytology*
  • Stress, Mechanical
  • Ureteral Obstruction / pathology

Substances

  • Caspase Inhibitors
  • HSP70 Heat-Shock Proteins
  • Caspases