title: Numb protects renal proximal tubular cells from puromycin aminonucleoside-induced apoptosis through inhibiting Notch signaling pathway.
abstract: Numb was originally discovered as an intrinsic cell fate determinant 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 antagonizing Notch signaling activity.
authors: Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Xuebing
authors: X
authors: Ding
authors: Fengxin
authors: F
authors: Zhu
authors: Tang
authors: T
authors: Li
authors: Qiugen
authors: Q
authors: Zhou
authors: Fan Fan
authors: FF
authors: Hou
authors: Jing
authors: J
authors: Nie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D011692:Puromycin Aminonucleoside / Q000494:pharmacology*; D034622:RNA Interference; D051381:Rats; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D051880:Receptors, Notch; C559994:numb protein, rat; D011692:Puromycin Aminonucleoside; D053148:Caspase 3