Justo Pilar, Sanz Ana, Lorz Corina, Gómez-Garre Dulcenombre, Mezzano Sergio, Egido Jesús, Ortiz Alberto
Fundación Jiménez Díaz, IRSIN, Madrid, Spain.
Kidney Int Suppl. 2003 Oct(86):S52-6. doi: 10.1046/j.1523-1755.64.s86.10.x.
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).
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).
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.
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.
细胞凋亡在肾损伤过程中导致肾小管细胞丢失。然而，调节肾小管细胞凋亡的机制尚未完全阐明。Smac/Diablo是一种线粒体蛋白，在细胞凋亡时释放到细胞质中，在那里它可阻断凋亡抑制蛋白（IAPs）的抗凋亡活性。
我们研究了在小鼠中毒性急性肾小管坏死以及暴露于致死性细胞因子肿瘤坏死因子（TNF）的培养肾小管上皮细胞中Smac/Diablo mRNA和蛋白表达的调节情况。
叶酸诱导的急性肾衰竭与肾小管细胞凋亡相关。Smac/Diablo mRNA和蛋白水平在24小时时增加了50%。TNF是一种在叶酸肾病中肾表达增加的细胞因子，它以时间依赖性方式诱导培养的肾小管上皮细胞凋亡。此外，TNF增加了Smac/Diablo的mRNA和蛋白表达。
这些发现支持这样一种观点，即Smac/Diablo mRNA和蛋白表达的调节是一种机制，通过该机制致死性刺激可增强其在肾细胞中的致死潜能。
