Abstract
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.
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Abbreviations
- XBP1:
-
X-box binding protein
- MEF:
-
Mouse embryonic fibroblast
- ER:
-
Endoplasmic reticulum
- HSF1:
-
Heat shock transcription factor
- eIF2:
-
Eukaryote initiation factor 2
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Acknowledgments
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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Yaohua Liu and Hiroaki Sakamoto contributed equally to this work.
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Liu, Y., Sakamoto, H., Adachi, M. et al. Heat stress activates ER stress signals which suppress the heat shock response, an effect occurring preferentially in the cortex in rats. Mol Biol Rep 39, 3987–3993 (2012). https://doi.org/10.1007/s11033-011-1179-2
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DOI: https://doi.org/10.1007/s11033-011-1179-2