Autophagy and protein aggregation after brain ischemia

Chunli Liu, Yanqin Gao, John Barrett, Bingren Hu

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Autophagy is the main degradation pathway responsible for eliminating abnormal protein aggregates and damaged organelles prevalent in neurons after transient cerebral ischemia. This study investigated whether accumulation of protein aggregate-associated organelles in post-ischemic neurons is a consequence of changes in autophagy. Electron microscopic analysis indicated that both autophagosomes and autolysosomes are significantly up-regulated in hippocampal CA1 and DG neurons after ischemia. The microtubule-associated protein light chain 3 (LC3)-II conjugate, a marker for autophagosomes assessed by western blotting, was up-regulated in post-ischemic brain tissues. Confocal microscopy showed that LC3 isoforms were located in living post-ischemic neurons. Treatment with chloriquine resulted in accumulation of LC3-II in sham-operated rats, but did not further change the LC3-II levels in post-ischemic brain tissues. The results indicate that at least part of the accumulation of protein aggregate-associated organelles seen following ischemia is likely to be because of failure of the autophagy pathway. The resulting protein aggregation on subcellular organelle membranes could lead to multiple organelle damage and to delayed neuronal death after transient cerebral ischemia.

Original languageEnglish
Pages (from-to)68-78
Number of pages11
JournalJournal of Neurochemistry
Volume115
Issue number1
DOIs
StatePublished - Oct 1 2010

Fingerprint

Autophagy
Brain Ischemia
Organelles
Neurons
Brain
Agglomeration
Light
Transient Ischemic Attack
Proteins
Tissue
Ischemia
Microtubule-Associated Proteins
Confocal microscopy
Rats
Protein Isoforms
Confocal Microscopy
Membranes
Degradation
Western Blotting
Electrons

Keywords

  • ATG12-ATG5 and LC3II
  • autophagy
  • brain ischemia
  • delayed neuronal death
  • electron microscopy
  • protein aggregation
  • protein misfolding
  • proteosome
  • ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Autophagy and protein aggregation after brain ischemia. / Liu, Chunli; Gao, Yanqin; Barrett, John; Hu, Bingren.

In: Journal of Neurochemistry, Vol. 115, No. 1, 01.10.2010, p. 68-78.

Research output: Contribution to journalArticle

Liu, Chunli ; Gao, Yanqin ; Barrett, John ; Hu, Bingren. / Autophagy and protein aggregation after brain ischemia. In: Journal of Neurochemistry. 2010 ; Vol. 115, No. 1. pp. 68-78.
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