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Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain
Authors:Wheeler Derek S  Dunsmore Katherine E  Wong Hector R
Institution:Division of Critical Care Medicine-OSB5, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45244, USA.
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.
Keywords:Heat shock protein (hsp)-70  Tat  Heat shock response  Protein transduction  Hyperoxia  Heat shock factor
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