Heat stress activates ER stress signals which suppress the heat shock response, an effect occurring preferentially in the cortex in rats
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Although heat stress induces a variety of illnesses, there have been few studies designed to uncover the molecular mechanisms underlining the illnesses. We here demonstrate that heat activates ER stress, which inhibits heat shock responses (HSR) via translational block. In heat-stressed rats, ER stress responses, as represented by eIF2α phosphorylation and XBP1 splicing, occurred mainly in the cortex, where the HSR was substantially inhibited. Heat exposure also activated ER stress signals in primary cortical neurons. Since HSF1 knockdown enhanced heat-induced ER stress and subsequent cell death, HSR inhibition in turn augments ER stress, implying a vicious spiral of both stresses. Taken together, heat-induced ER stress impairs the HSR and enhances cell damage, thereby manifesting its unique effect on heat stress.
KeywordsHeat shock HSF1 ER stress XBP1 eIF2α
X-box binding protein
Mouse embryonic fibroblast
Heat shock transcription factor
Eukaryote initiation factor 2
Supported in part by grants from the Ministry of Education, Culture, Sports, Science, Japan (to M.A, M.H., K.I., Y.S.). We are grateful to Dr. Peter M Olley (Sapporo Medical University School of Medicine) for editorial help.
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