期刊
NEUROCHEMICAL RESEARCH
卷 32, 期 12, 页码 2006-2014出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-007-9318-9
关键词
calpain; cytoskeleton; neurofilament; optic nerve; spectrin; tubulin; white matter
资金
- NINDS NIH HHS [P50-NS08803, R01-NS45131, T32-NS043126, R01 NS048234-01A2, R01-NS41561, R01 NS048234] Funding Source: Medline
To examine the time course and relative extent of proteolysis of neurofilament and tubulin proteins after traumatic axonal injury (TAI), anesthetized mice were subjected to optic nerve stretch injury. Immunohistochemistry confirmed neurofilament accumulation within axonal swellings at 4, 24, and 72 h postinjury (n = 4 injured and 2 sham per time point). Immunoblotting of optic nerve homogenates (n = 5 injured and 1 sham at 0.5, 4, 24 or 72 h) revealed calpain-mediated spectrin proteolytic fragments after injury. Protein levels for NF68 progressively decreased from 0.5 h to 24 h postinjury, while NF200 and alpha-tubulin levels decreased acutely (0.5-4 h), with a secondary decline at 72 h postinjury. These data demonstrate that diffusely distributed TAI is associated not only with a localized accumulation of neurofilament proteins, but also significant decreases in total cytoskeletal protein levels which may be mediated, in part, by calpains. Protection of the axonal cytoskeleton represents a potential therapeutic target for axonal damage associated with injury or neurodegenerative diseases.
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