Portal de Periódicos da CAPES

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

2004; Lippincott Williams & Wilkins; Volume: 171; Issue: 1 Linguagem: Inglês

10.1097/01.ju.0000091106.61065.e3

1527-3792

Richard Power, Belinda T. Doyle, Debra F. Higgins, Hugh R. Brady, John M. Fitzpatrick, R. William G. Watson,

Spaceflight effects on biology

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jan 2004Mechanical Deformation Induced Apoptosis in Human Proximal Renal Tubular Epithelial Cells is Caspase Dependent RICHARD E. POWER, BELINDA T. DOYLE, DEBRA HIGGINS, HUGH R. BRADY, JOHN M. FITZPATRICK, and R. WILLIAM G. WATSON RICHARD E. POWERRICHARD E. POWER , BELINDA T. DOYLEBELINDA T. DOYLE , DEBRA HIGGINSDEBRA HIGGINS , HUGH R. BRADYHUGH R. BRADY , JOHN M. FITZPATRICKJOHN M. FITZPATRICK , and R. WILLIAM G. WATSONR. WILLIAM G. WATSON View All Author Informationhttps://doi.org/10.1097/01.ju.0000091106.61065.e3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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-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 pathway to protect against renal tubular cell apoptosis and the potential for progression to renal failure in UO. References 1 : Renal haemodynamics and prostaglandin synthesis in partial unilateral ureteric obstruction. Urol Res1994; 22: 279. Google Scholar 2 : Cell apoptosis and proliferation in experimental chronic obstructive uropathy. Kidney Int1996; 50: 200. Google Scholar 3 : Renal perfusion and intratubular pressure during ureteral occlusion in the rat. Am J Physiol1980; 238: F205. Google Scholar 4 : Mechanism of acute hemodynamic response to ureteral occlusion. Invest Urol1971; 9: 109. Google Scholar 5 : Genesis of renal tubular atrophy in experimental hydronephrosis in the rat. Role of apoptosis. Lab Invest1987; 56: 273. Google Scholar 6 : Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney Int1995; 47: 1285. Google Scholar 7 : Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int2000; 58: 2301. Google Scholar 8 : Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction. Kidney Int2001; 59: 1290. Google Scholar 9 : Response of porcine aortic smooth muscle to cyclic tensional deformation in culture. J Surg Res1988; 44: 696. Google Scholar 10 : Chronic ureteral obstruction in the rat suppresses renal tubular Bcl-2 and stimulates apoptosis. Exp Nephrol2000; 8: 115. Google Scholar 11 : Nitric oxide in unilateral ureteral obstruction: effect on regional renal blood flow. Kidney Int2001; 59: 1059. Crossref, Medline, Google Scholar 12 : Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest1998; 101: 1326. Google Scholar 13 : Recent progress in studies on osteocytes—osteocytes and mechanical stress. Kaibogaku Zasshi2000; 75: 451. Google Scholar 14 : Renal cell apoptosis in chronic obstructive uropathy: the roles of caspases. Kidney Int2001; 60: 924. Google Scholar 15 : Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol2000; 2: 469. Google Scholar 16 : Increased heat shock protein-70 in unilateral ureteral obstruction in rats. Mol Genet Metab1998; 65: 303. Google Scholar 17 : Expression of hsp 27, hsp 60, hsc 70, and hsp 70 by immortalized human proximal tubule cells (HK-2) following exposure to heat shock, sodium arsenite, or cadmium chloride. J Toxicol Environ Health A2001; 63: 475. Google Scholar 18 : PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis. Eur J Neurosci2002; 15: 1451. Google Scholar From the Departments of Surgery (REP, BTD, JMF, RWGW) and Medicine and Therapeutics (DH, HRB), Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research and Dublin Molecular Medicine Centre, University College Dublin, Dublin, Ireland© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: Activation of HIF2α in Kidney Proximal Tubule Cells Causes Abnormal Glycogen Deposition but Not TumorigenesisJournal of Urology, VOL. 191, NO. 2, (555-555), Online publication date: 1-Feb-2014. Volume 171Issue 1January 2004Page: 457-461 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordscaspasesheat-shock proteins 70apoptosisureteral obstructionureterMetricsAuthor Information RICHARD E. POWER More articles by this author BELINDA T. DOYLE More articles by this author DEBRA HIGGINS More articles by this author HUGH R. BRADY More articles by this author JOHN M. FITZPATRICK More articles by this author R. WILLIAM G. WATSON More articles by this author Expand All Advertisement PDF downloadLoading ...