Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux.
Exp Cell Res
; 358(2): 147-160, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28624412
ABSTRACT
Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Autofagia
/
Glucose
/
Hipotermia
/
Lisossomos
Limite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China