title: Numb/Notch signaling plays an important role in cerebral ischemia-induced apoptosis.
abstract: Numb has been shown to play diverse roles in the central nervous system of adult mammals, and accumulating evidence indicates a role for Numb in apoptosis. In this study, we characterize the role of Numb in ischemia-induced apoptosis, and investigate the underlying pathway involved in this process. In vivo, exposure of pheochromocytoma (PC12) cells to glucose deprivation (GD) resulted in caspase-3-dependent apoptosis. Numb expression was upregulated by GD in a time-dependent manner, while Notch expression was down regulated. Knocking down endogenous Numb expression via siRNA protected PC12 cells from GD-induced apoptosis, whereas Numb overexpression sensitized PC12 cells to GD-induced apoptosis. In vivo, significantly increased Numb expression levels, together with activation of apoptosis, can be observed in the ischemic penumbra following cerebral ischemia. Taken together, our data show that Numb promotes ischemia-induced apoptosis. Based on these results, we conclude that inhibition of Numb could be a novel therapeutic approach for inhibiting apoptosis in the ischemic penumbra.
authors.affiliation: Department of Neurology, Henan Provincial People's Hospital, No.7, Weiwu Road, Zhengzhou 450003, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
authors.forename: Xuejing
authors.initials: X
authors.lastname: Wang
authors.forename: Xuebing
authors.initials: X
authors.lastname: Ding
authors.forename: Junfang
authors.initials: J
authors.lastname: Teng
authors.forename: Fengmin
authors.initials: F
authors.lastname: Shao
authors.forename: Jiewen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D015536:Down-Regulation / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; C559994:numb protein, rat; D005947:Glucose