Chaperone-mediated autophagy after traumatic brain injury

Yujung Park, Chunli Liu, Tianfei Luo, W. Dalton Dietrich, Helen Bramlett, Bingren Hu

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Chaperone-mediated autophagy (CMA) and the ubiquitin-proteasomal system (UPS) are two major protein degradation systems responsible for maintaining cellular homeostasis, but how these two systems are regulated after traumatic brain injury (TBI) remains unknown. TBI produces primary mechanical damage that must be repaired to maintain neuronal homeostasis. The level of lysosomal-associated membrane protein type 2A (LAMP2A) is the hallmark of CMA activity. The level of polyubiquitinated proteins (ubi-proteins) reflects UPS activity. This study utilized a moderate fluid percussion injury model in rats to investigate the changes in CMA and the UPS after TBI. Induction of CMA was manifested by significant upregulation of LAMP2A and secondary lysosomes during the periods of 1-15 days of recovery after TBI. In comparison, the levels of ubi-proteins were increased only moderately after TBI. The increases in the levels of LAMP2A and 70kDa heat-shock protein for CMA after TBI were seen mainly in the secondary lysosome-containing fractions. Confocal and electron microscopy further showed that increased LAMP2A or lysosomes were found mainly in neurons and proliferated microglia. Because CMA and the UPS are two major routes for elimination of different types of cellular aberrant proteins, the consecutive activation of these two pathways may serve as a protective mechanism for maintaining cellular homeostasis after TBI.

Original languageEnglish (US)
Pages (from-to)1449-1457
Number of pages9
JournalJournal of neurotrauma
Volume32
Issue number19
DOIs
StatePublished - Oct 1 2015

Keywords

  • HSC70
  • HSP70
  • Iba-1
  • LAMP2
  • chaperone-mediated autophagy
  • lysosome
  • traumatic brain injury
  • ubiquitin

ASJC Scopus subject areas

  • Clinical Neurology

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