Mechanical Deformation Induced Apoptosis in Human Proximal Renal Tubular Epithelial Cells is Caspase Dependent
| Autor: | Hugh R. Brady, Debra F. Higgins, John M. Fitzpatrick, Richard E. Power, R. William G. Watson, Belinda T. Doyle |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Urology Apoptosis Caspase 3 Kidney Tubules Proximal Internal medicine Heat shock protein medicine Humans HSP70 Heat-Shock Proteins Viability assay Cells Cultured Caspase biology Epithelial Cells Caspase Inhibitors Hsp70 Cell biology Endocrinology Caspases biology.protein Tumor necrosis factor alpha Stress Mechanical Ureteral Obstruction |
| Zdroj: | Journal of Urology. 171:457-461 |
| ISSN: | 1527-3792 0022-5347 |
| DOI: | 10.1097/01.ju.0000091106.61065.e3 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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