Heat shock protects cultured neurons from glutamate toxicity.
Expression of heat shock proteins (HSPs) occurs in brain after ischemia and status epilepticus. We report that induction of the heat shock response in cortical cultures protects neurons from glutamate-induced excitotoxicity. Cultures heated to 42.2 degrees C for 20 min showed an overall decrease in protein synthesis but an increase in the synthesis of approximately 72 and approximately 85 kd proteins and in the levels of HSP70 mRNA. Heat shock inhibited excitotoxicity in cells exposed to glutamate at 3 or 24 hr following heat exposure, but not when the interval between heat and glutamate exposure was shortened to 15 min or lengthened to 48 hr. Protection due to heat shock required new protein synthesis, since it did not occur when protein or RNA synthesis inhibitors were added. By ameliorating excitotoxic processes, HSPs may attenuate brain injury in certain pathologic conditions.
Rordorf
G
G
Stroke Research Center, Massachusetts General Hospital, Boston.
Koroshetz
W J
WJ
Bonventre
J V
JV
D000818:Animals; D015152:Blotting, Northern; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D005971:Glutamates; D006360:Heat-Shock Proteins; D009498:Neurotoxins; D003609:Dactinomycin; D018698:Glutamic Acid; D012313:RNA; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase