Journal
EXPERIMENTAL CELL RESEARCH
Volume 358, Issue 2, Pages 147-160Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2017.06.010
Keywords
Mild hypothermia; OGD/R; Lysosomal function; Autophagic flux
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Funding
- Medical Research Fund of Guangdong Province [A2015392]
- National Natural Science Foundation of China [81503052]
- Public Welfare Research and Capacity Building Project of Guangdong Province [2014A020212164]
- Basic and Applied Basic Research Project of Guangdong Province [2016A030313322]
- Guangzhou Science and Technology Research Project [201607010219]
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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.
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