title: Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain.
abstract: 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.
authors.affiliation: Division of Critical Care Medicine-OSB5, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45244, USA.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Wheeler
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Dunsmore
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010100:Oxygen / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014161:Transduction, Genetic
chemical_list: D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D010100:Oxygen