title: Heat Acclimation Regulates the Autophagy-Lysosome Function to Protect Against Heat Stroke-Induced Brain Injury in Mice.
abstract: OBJECTIVE
  The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear.
  
  
  METHODS
  The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS. The effects of HA on autophagy and lysosomes were assessed in the presence of the autophagy inhibitor 3-methyladenine (3MA). Autophagy and lysosome-associated proteins were analysed by Western blotting.
  
  
  RESULTS
  We found that HA protected against HS-induced death and brain injury. HS can robustly induce autophagy and impair lysosome function. HA pre-conditioning significantly modulated the autophagy level, and improved lysosome function in HS mice. Furthermore, 3MA completely abolished the neuroprotective effect of HA on HS.
  
  
  CONCLUSIONS
  HS may induce brain injury through lysosomal dysfunction and impaired autophagic flux. HA protected against HS-induced brain injury via a mechanism involving the autophagy-lysosome pathway.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Yi
authors.forename: Genlin
authors.initials: G
authors.lastname: He
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.forename: Xuesen
authors.initials: X
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Luo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002401:Cathepsin B / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018883:Heat Stroke / Q000150:complications; D006358:Hot Temperature; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015996:Survival Rate; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000225:Adenine; D000071186:Beclin-1; D002401:Cathepsin B; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C025946:3-methyladenine
keywords: Autophagy; Brain injury; Heat acclimation; Heat stroke; Lysosome