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 language | English |
|---|---|
| Pages (from-to) | 68-78 |
| Number of pages | 11 |
| Journal | Journal of Neurochemistry |
| Volume | 115 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 1 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Autophagy and protein aggregation after brain ischemia
AU - Liu, Chunli
AU - Gao, Yanqin
AU - Barrett, John
AU - Hu, Bingren
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
KW - ATG12-ATG5 and LC3II
KW - autophagy
KW - brain ischemia
KW - delayed neuronal death
KW - electron microscopy
KW - protein aggregation
KW - protein misfolding
KW - proteosome
KW - ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=77956562189&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956562189&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2010.06905.x
DO - 10.1111/j.1471-4159.2010.06905.x
M3 - Article
C2 - 20633207
AN - SCOPUS:77956562189
VL - 115
SP - 68
EP - 78
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 1
ER -