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. CONCLUSION: 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.[1]References
- Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure. Justo, P., Sanz, A., Lorz, C., Gómez-Garre, D., Mezzano, S., Egido, J., Ortiz, A. Kidney Int. Suppl. (2003) [Pubmed]
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