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Tat-Collapsin Response Mediator Protein 2 (CRMP2) Increases the Survival of Neurons After NMDA Excitotoxity by Reducing the Cleavage of CRMP2

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Abstract

Collapsin response mediator protein 2 (CRMP2) is a brain-specific multifunctional adaptor protein involved in neuronal polarity and axonal guidance. Our previous results showed CRMP2 may be involved in the hypoxic preconditioning and ischemic injury, but the mechanism was not clear. This study explored whether CRMP2 was involved in NMDA-induced neural death, and the possible mechanism. Western blot analysis demonstrated that NMDA reduced the phosphorylation of CRMP2 and inspired the cleavage of CRMP2. Also, it was detected that NMDA treatment did not affect the phosphorylation of CRMP2 in early stage (<6 h). Over-expression of CRMP2 aggravated the NMDA-induced injury, suggesting the vital role of CRMP2 in excitotoxicity. Tat-CRMP2 was designed to provide the cleavage site of calpain. Thiazolyl blue tetrazolium bromide assay, Hoechst33342/Propidium Iodide staining and Western blot assay showed that Tat-CRMP2 pretreatment increased cell viability compared with the control group against NMDA exposure by decreasing the cleavage of CRMP2. In conclusion, these studies indicated that cleavage of CRMP2 plays an important role involved in the NMDA-induced injury. The cleavage of CRMP2 may be a promising target for excitatory amino acid-related ischemic and hypoxic injury.

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Acknowledgments

This work was supported by the following grants: National Natural Science Foundation of China (30871219, 31200895, 31071048), China 973 Pre-program (2011CB512109), Ph.D. Programs Foundation of Ministry of Education of China (20091107110001).

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Authors and Affiliations

  1. Department of Neurobiology and Beijing Institute for Brain Disorders, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People’s Republic of China

    Yanling Yin, Lumian Chen, Song Han, Li Zhao, Yanlin Luo & Junfa Li

  2. Department of Spine Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province, People’s Republic of China

    Yansong Wang

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  1. Yanling Yin
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Correspondence to Junfa Li.

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Yin, Y., Wang, Y., Chen, L. et al. Tat-Collapsin Response Mediator Protein 2 (CRMP2) Increases the Survival of Neurons After NMDA Excitotoxity by Reducing the Cleavage of CRMP2. Neurochem Res 38, 2095–2104 (2013). https://doi.org/10.1007/s11064-013-1118-9

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