Mechanical Deformation Induced Apoptosis in Human Proximal Renal Tubular Epithelial Cells is Caspase Dependent

ABSTRACTPurpose: 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-α 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 pa...