title: Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure.
abstract: BACKGROUND
  Apoptosis contributes to tubular cell loss in the course of renal injury. However, the mechanisms regulating tubular cell apoptosis are not well understood. Smac/Diablo is a mitochondrial protein that is released to the cytosol during apoptosis, where it blocks the antiapoptotic activity of inhibitor of apoptosis proteins (IAPs).
  
  
  METHODS
  We have studied the regulation of Smac/Diablo mRNA and protein expression in murine toxic acute tubular necrosis, and in cultured tubular epithelial cells exposed to the lethal cytokine tumor necrosis factor (TNF).
  
  
  RESULTS
  Folic acid-induced acute renal failure was associated with tubular cell apoptosis. Smac/Diablo mRNA and protein levels increased by 50% at 24 hours. TNF, a cytokine whose renal expression increases in folic acid nephropathy, induced apoptosis in cultured tubular epithelial cells in a time-dependent manner. In addition, TNF increased the mRNA and protein expression of Smac/Diablo.
  
  
  CONCLUSIONS
  These findings support the concept that regulation of Smac/Diablo mRNA and protein expression is a mechanism by which lethal stimuli amplify their lethal potential in renal cells.
authors.affiliation: Fundación Jiménez Díaz, IRSIN, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Justo
authors.forename: Ana
authors.initials: A
authors.lastname: Sanz
authors.forename: Corina
authors.initials: C
authors.lastname: Lorz
authors.forename: Dulcenombre
authors.initials: D
authors.lastname: Gómez-Garre
authors.forename: Sergio
authors.initials: S
authors.lastname: Mezzano
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005492:Folic Acid; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C499605:Diablo protein, mouse; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005492:Folic Acid