Numb Protects Renal Proximal Tubular Cells from Puromycin Aminonucleoside-Induced Apoptosis through Inhibiting Notch Signaling Pathway

Numb Protects Renal Proximal Tubular Cells from Puromycin Aminonucleoside-Induced Apoptosis through Inhibiting Notch Signaling Pathway

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Numb was originally discovered as an intrinsic cell fate determinant g5210t-p90 in Drosophila by antagonizing Notch signaling.The present study is to characterize the role of Numb in oxidative stress-induced apoptosis of renal proximal tubular cells.Exposure of NRK52E cells to puromycin aminonucleoside (PA) resulted in caspase 3-dependent apoptosis.Numb expression was downregulated by PA in a time- and dose-dependent manner.Knocking down endogenous Numb by siRNA sensitized NRK52E cells to PA-induced apoptosis, whereas overexpressing Numb protected NRK52E cells from PA-induced apoptosis.

Moreover, PA activated Notch signaling in a time- and dose-dependent manner as indicated by increased expression of the intracellular domain of Notch and Hes-1.Notch signaling inhibitor DAPT significantly attenuated Numb siRNA-augmented apoptosis.On the other hand, overexpression of intracellular domain of Notch1 could reverse the protective effect of Numb on PA-induced apoptosis.Taken together, our data demonstrated that, in renal proximal tubular cells, Numb functions as a protective molecule on PA-induced apoptosis through Sneakers for Men - Grey - Canvas Mesh Athletic Running Shoes antagonizing Notch signaling activity.