Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain

Heat shock protein 70 (HSP70) is an intracellular stress protein that confers cytoprotection to a variety of cellular stressors. Several lines of evidence have suggested that augmentation of the heat shock response by increasing the expression of HSP70 represents a potential therapeutic strategy for...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-01, Vol.301 (1), p.54-59
Main Authors: Wheeler, Derek S, Dunsmore, Katherine E, Wong, Hector R
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Survival
DNA-Binding Proteins - genetics
Gene Products, tat - chemistry
Gene Products, tat - genetics
Gene Products, tat - metabolism
Heat shock factor
Heat shock protein (hsp)-70
Heat shock response
Heat Shock Transcription Factors
Hot Temperature
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - metabolism
Humans
Hyperoxia
Mice
Mice, Knockout
Oxygen - metabolism
Protein transduction
Protein Transport - physiology
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Tat
Transcription Factors
Transduction, Genetic
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Summary:Heat shock protein 70 (HSP70) is an intracellular stress protein that confers cytoprotection to a variety of cellular stressors. Several lines of evidence have suggested that augmentation of the heat shock response by increasing the expression of HSP70 represents a potential therapeutic strategy for the treatment of critically ill patients. The Tat protein of human immunodeficiency virus 1 (HIV-1) has been used previously to deliver functional cargo proteins intracellularly when added exogenously to cultured cells. We generated a Tat-HSP70 fusion protein using recombinant methods and treated HSF −/− cells with either Tat-HSP70 or recombinant HSP70 prior to exposure to hyperoxia or lethal heat shock. We showed that biologically active, exogenous HSP70 can be delivered into cells using the HIV-1 Tat protein, and that the Tat-mediated delivery of HSP70 confers cytoprotection against thermal stress and hyperoxia and may represent a novel approach to augmenting intracellular HSP70 levels.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)02986-8