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Numb/Notch Signaling Plays an Important Role in Cerebral Ischemia-induced Apoptosis

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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.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (81100881, 81100949).

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Authors and Affiliations

  1. Department of Neurology, Henan Provincial People’s Hospital, No.7, Weiwu Road, Zhengzhou, 450003, China

    Mingming Ma & Jiewen Zhang

  2. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Xuejing Wang & Junfang Teng

  3. Department of Nephrology, Henan Provincial People’s Hospital, Zhengzhou, China

    Xuebing Ding & Fengmin Shao

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  1. Mingming Ma
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Correspondence to Jiewen Zhang.

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Ma, M., Wang, X., Ding, X. et al. Numb/Notch Signaling Plays an Important Role in Cerebral Ischemia-induced Apoptosis. Neurochem Res 38, 254–261 (2013). https://doi.org/10.1007/s11064-012-0914-y

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  • DOI: https://doi.org/10.1007/s11064-012-0914-y

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