期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 28, 期 4, 页码 674-683出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/sj.jcbfm.9600587
关键词
ATG12-ATG5; autophagy; LC3-ATG8-APG8; lysosome; traumatic brain injury; ubiquitin
资金
- NINDS NIH HHS [P50 NS030291, NS36810, NS040407, NS030291, R01 NS040407-08, R01 NS040407, R56 NS036810, R01 NS036810, R29 NS036810] Funding Source: Medline
Autophagy is the chief machinery for bulk degradation of superfluous or aberrant cytoplasmic components. This study used the rat moderate fluid percussion injury model to investigate whether the autophagy pathway plays a key role after traumatic brain injury (TBI). Induction of autophagy is manifested by accumulation of autophagosomes (APs), observable under transmission electron microscopy (EM). Two hallmarks of autophagy, i. e., the microtubule-associated protein light chain 3 (LC3)-II and the autophagy-related gene (ATG) 12-ATG5 conjugates, were explored by biochemical and confocal microscopic analyses of brain tissues. Under EM, both APs and autolysosomes were markedly accumulated in neurons from 4 h onward after TBI. Western blot analysis showed that ATG12-ATG5 conjugate was markedly redistributed during 5 to 15 days in brain tissues after TBI. LC3-II conjugate was initially unchanged but was drastically upregulated from 24 h onward in the pre-AP-containing fraction after TBI. LC-3 immunostaining was mainly located in living neurons under confocal microscopy. These results clearly show that the autophagy pathway is persistently activated after TBI. Because the autophagy pathway is the chief machinery for bulk elimination of aberrant cell components, we propose that activation of this pathway serves as a protective mechanism for maintaining cellular homeostasis after TBI.
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