title: JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells.
abstract: OBJECTIVE
  In renal epithelial cells, mechanical forces produced from urinary obstruction serve as potential mediators of apoptosis by activating specific intracellular signaling pathways. In this study, we sought to further define the role of JNK and p38 SAPK-2 pathway and caspase activation in stretch-induced apoptosis.
  
  
  METHODS
  Immortalized cell lines derived from the various components of the nephron were subjected to cyclical stretch and their differential apoptotic response was assessed. Pharmacologic inhibitors and Western blot analysis were used to assess the involvement of the MAPK pathways. Caspases' activity was assessed with ELISA and by Western blot analysis.
  
  
  RESULTS
  Stretch-induced apoptosis was dependent upon the cell phenotype and the degree of stretch. In NRK-52E cells, it was mediated through both JNK and p38 SAPK-2 pathways, and inhibition of either pathway reduced the degree of stretch-induced apoptosis. Stretched cells showed increased activity of caspase-3 and -9 but not -2 or -8. Stretch-induced apoptosis was modulated by inhibition of caspase-3 and to a lesser extent by caspase-9.
  
  
  CONCLUSIONS
  These findings suggest that stretch induces apoptosis in renal epithelial cells through the specific activation of JNK/SAPK and p38 SAPK-2 pathways and is dependent on the activation of caspase-3 and -9.
authors.affiliation: Department of Urology, University of California, San Francisco, California, USA. hiep.nguyen@childrens.harvard.edu
authors.forename: Hiep T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Anna
authors.initials: A
authors.lastname: Gaborro
authors.forename: Bradford
authors.initials: B
authors.lastname: Tinloy
authors.forename: Courtney
authors.initials: C
authors.lastname: Phillips
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D051379:Mice; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; C506434:Casp9 protein, mouse; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases