Nuclear translocation and aggregate formation of heat shock cognate protein 70 (Hsc70) in oxidative stress and apoptosis.
Recent evidence has shown a role for the heat shock cognate protein Hsc70 in the response to oxidative stress. We have investigated the subcellular distribution of Hsc70 by means of laser scanning confocal microscopy in neuroblastoma NB41A3 cells, in fibroblasts R6 cells and in R6-Bcl-2, an apoptosis-resistant cell line, and its function in oxidative stress and in apoptosis has been evaluated. Endogenous Hsc70 is localised predominantly in the cytoplasm in unstressed cells, whereas oxidative stress but not apoptosis induces its translocation into the nucleus. In transfected cells overexpressing Hsc70 increased nuclear translocation and aggregation of Hsc70 in intracellular speckles is observed after oxidative stress and, to a lesser degree, after exposure to apoptotic agents. Bcl-2 did not influence the movement of Hsc70 nor the formation of Hsc70-containing speckles. Nuclear translocation of Hsc70 can be modulated by the expression of components from a previously described plasma membrane oxidoreductase involved in the cellular response against oxidative stress. Our data may suggest a correlation between differential translocation of Hsc70 with specific functions in apoptosis and a potential role in the protection against reactive oxygen species.
Institute of Biochemistry, University of Fribourg, CH-1700 Fribourg, Switzerland.
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Z
Dastoor
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Dreyer
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D016543:Central Nervous System Neoplasms; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D049452:Green Fluorescent Proteins