Abstract | OBJECTIVE: To investigate the activity of collapsin response mediator protein 2 (CRMP-2) and its possible regulation for axonal and dendrictic injury under hypoxia- ischemia (HI). METHODS: Postnatal day 10 SD rats were suffered the right common carotid artery ligation and 8% mixture of oxygen and nitrogen hypoxia 2.5 h to produce HI model. The expression of total and phosphorylated CRMP-2 and amyloid precursor protein (APP) were detected by Western blot after HI. After pretreatment of protein kinase B (Akt) inhibitor, wortmannin or LY294002, western blot and immunohistochemistry were applied to detect the expression of total and phosphorylated of CRMP-2 at 4 h and 24 h after HI. At 72 h after HI, APP was detected by Western blot and immunohistochemistry, axonal and dendrictic injury was determined by electron microscope. RESULTS: Total CRMP-2 was not obviously changed after HI, compared with that of sham controls. However, the phosphorylated CRMP-2 (p-CRMP-2) protein transiently increased at 0.5 h, started to decrease at 2 h, remained at a low level at the rest of the time points, compared with that of sham controls. APP protein started to increase at 2 h, remained at a high level at 4, 8, 24 h, and then progressively increased at 48 and 72 h. In wortmannin and LY294002 group, CRMP-2 protein was not obviously changed at 4 h and 24 h after HI. However, p-CRMP-2 increased at 4 h and 24 h. At 72 h, wortmannin pretreatment increased APP expression, leading to more severe ultrastructure failure of axon and dendrite. CONCLUSION: As a downstream effector of Akt pathway, CRMP-2 is involved in axonal and dendritic injury regulation after HI in neonatal rat.
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Authors | Tao Xiong, Hong-ju Chen, Yi Qu, De-zhi Mu |
Journal | Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition
(Sichuan Da Xue Xue Bao Yi Xue Ban)
Vol. 46
Issue 4
Pg. 513-8
(Jul 2015)
ISSN: 1672-173X [Print] China |
PMID | 26480649
(Publication Type: Journal Article)
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Chemical References |
- Chromones
- Intercellular Signaling Peptides and Proteins
- Morpholines
- Nerve Tissue Proteins
- collapsin response mediator protein-2
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Topics |
- Animals
- Animals, Newborn
- Axons
(metabolism, pathology)
- Blotting, Western
- Chromones
- Dendrites
(metabolism, pathology)
- Hypoxia
- Hypoxia-Ischemia, Brain
(metabolism)
- Immunohistochemistry
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Morpholines
- Nerve Tissue Proteins
(metabolism)
- Phosphorylation
- Rats
- Rats, Sprague-Dawley
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