Delivery of a constitutively active form of the heat shock factor using a virus vector protects neuronal cells from thermal or ischaemic stress but not from apoptosis

Authors

  • M. J. D. Wagstaff,

    1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, Windeyer Building, Cleveland Street, London W1P 6DB, UK
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  • J. Smith,

    1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, Windeyer Building, Cleveland Street, London W1P 6DB, UK
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  • Y. Collaco-Moraes,

    1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, Windeyer Building, Cleveland Street, London W1P 6DB, UK
    2. Department of Neuromuscular Diseases, Imperial College of Science Technology and Medicine, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK
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  • J. S. De Belleroche,

    1. Department of Neuromuscular Diseases, Imperial College of Science Technology and Medicine, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK
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  • R. Voellmy,

    1. Department of Biochemistry and Molecular Biology (R-629) University of Miami School of Medicine, 1011 NW 15th Street, Miami, FL 33136-1015, USA
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  • R. S. Coffin,

    1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, Windeyer Building, Cleveland Street, London W1P 6DB, UK
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  • D. S. Latchman

    1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, Windeyer Building, Cleveland Street, London W1P 6DB, UK
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D. S. Latchman, as above. E-mail: d.latchman@ucl.ac.uk

Abstract

The heat shock proteins (HSPs) are induced by stressful stimuli and have a protective effect. Different HSPs protect with different efficiencies against different stresses indicating that optimal protection would be obtained with a non-stressful agent which induced a range of HSPs. We have prepared a herpesvirus vector expressing a constitutively active mutant form of heat shock factor 1 (HSF1) which, unlike the wild-type form of this transcription factor, does not require stress for its activation. Upon infection of neuronal cells, this virus induced a more restricted range of HSPs than in non-neuronal cells. Infection with the virus protected neuronal cells against subsequent thermal or ischaemic stress in accordance with its ability to induce HSP70 expression but did not protect them against apoptotic stimuli. The mechanisms of these effects and their significance for the use of HSF to manipulate HSP gene expression is discussed.

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