title: Tat-collapsin response mediator protein 2 (CRMP2) increases the survival of neurons after NMDA excitotoxity by reducing the cleavage of CRMP2.
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.
authors.affiliation: 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.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yin
authors.forename: Yansong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lumian
authors.initials: L
authors.lastname: Chen
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Luo
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015696:Gene Products, tat / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D010766:Phosphorylation; D051381:Rats; D014162:Transfection
chemical_list: D015696:Gene Products, tat; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C095114:collapsin response mediator protein-2; D016202:N-Methylaspartate
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