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.
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.
Wagstaff
M J
MJ
Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London Medical School, UK.
Smith
J
J
Collaco-Moraes
Y
Y
de Belleroche
J S
JS
Voellmy
R
R
Coffin
R S
RS
Latchman
D S
DS
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005822:Genetic Vectors; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature / Q000009:adverse effects*; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics; D013126:Spinal Nerve Roots / Q000473:pathology; D013312:Stress, Physiological / Q000473:pathology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D014157:Transcription Factors