Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure.
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.
Justo
Pilar
P
Fundación Jiménez Díaz, IRSIN, Madrid, Spain.
Sanz
Ana
A
Lorz
Corina
C
Gómez-Garre
Dulcenombre
D
Mezzano
Sergio
S
Egido
Jesús
J
Ortiz
Alberto
A
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
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