Numb protects renal proximal tubular cells from puromycin aminonu-cleoside-induced apoptosis through inhibiting Notch signaling pathway

Abstract

Numb was originally discovered as an intrinsic cell fate determinant in Drosophila by antago-nizing 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 expres-sion was downregulated by PA in a time- and dose-dependent manner. Knocking down en-dogenous 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, overex-pression 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 antagonizing Notch signaling activity. © Ivyspring International Publisher.