Molecular Biology Reports

, Volume 39, Issue 4, pp 3987–3993 | Cite as

Heat stress activates ER stress signals which suppress the heat shock response, an effect occurring preferentially in the cortex in rats

  • Yaohua Liu
  • Hiroaki Sakamoto
  • Masaaki Adachi
  • Shiguang Zhao
  • Wataru Ukai
  • Eri Hashimoto
  • Masato Hareyama
  • Tadao Ishida
  • Kohzoh Imai
  • Yasuhisa Shinomura


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.


Heat shock HSF1 ER stress XBP1 eIF2α 



X-box binding protein


Mouse embryonic fibroblast


Endoplasmic reticulum


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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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Yaohua Liu
    • 1
    • 2
  • Hiroaki Sakamoto
    • 1
  • Masaaki Adachi
    • 1
  • Shiguang Zhao
    • 2
  • Wataru Ukai
    • 3
  • Eri Hashimoto
    • 3
  • Masato Hareyama
    • 4
  • Tadao Ishida
    • 1
  • Kohzoh Imai
    • 1
  • Yasuhisa Shinomura
    • 1
  1. 1.First Department of Internal MedicineSapporo Medical University School of MedicineSapporoJapan
  2. 2.Department of NeurosurgeryThe First Clinical College of Harbin Medical UniversityNangang, HarbinPeople’s Republic of China
  3. 3.Department of NeuropsychiatrySapporo Medical University School of MedicineSapporoJapan
  4. 4.Department of RadiologySapporo Medical University School of MedicineSapporoJapan

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