title: In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance.
abstract: Glial cells release a variety of molecules that support neuronal function. Because heat shock proteins (Hsps) are important in the survival of neurons subjected to metabolic stress, the possibility that glia can release the inducible form of the 70 kDa Hsp (Hsp70) was examined. Additionally, the ability of neuronal cells to show increased stress tolerance by taking up a mixture of constitutive and inducible forms of Hsp70 (Hsc/Hsp70) added to the extracellular fluid was tested. Human T98G glioma cells and differentiated LA-N-5 neuroblastoma cells were used as model glia and neurons to investigate these points. Hsp70 was analyzed using affinity chromatography, Western blotting, and immunofluorescence microscopy. The glioma cells were shown to export Hsp70 into the culture medium whether under normal conditions or subjected to heat shock. The amount of glial Hsp70 released ranged from 5 to 15 pg per 10(6) cells per day, being greater following heat shock. Neuroblastoma cells took up biotinylated Hsc/Hsp70 within 1 h after it was added to the culture medium and it made them more resistant to heat shock (44 degrees C) and to staurosporine-induced apoptosis. This increased stress tolerance was especially important in neuroblastoma cells induced to differentiate with phorbol ester because those 'mature neurons' showed a 10-fold decline in endogenous Hsp70, which was accompanied by increased susceptibility to heat shock and staurosporine-induced apoptosis. These results suggest that extracellular Hsp70 may provide a means by which glia can affect neuronal function, perhaps enhancing neuronal stress tolerance.
authors.affiliation: Laboratory of Cell Protection Mechanisms, Institute of Cytology Russian Academy of Science Tikhoretsky 4, 194064, St. Petersburg, Russia. guzhova@link.cytspb.rssi.ru
authors.forename: I
authors.initials: I
authors.lastname: Guzhova
authors.forename: K
authors.initials: K
authors.lastname: Kislyakova
authors.forename: O
authors.initials: O
authors.lastname: Moskaliova
authors.forename: I
authors.initials: I
authors.lastname: Fridlanskaya
authors.forename: M
authors.initials: M
authors.lastname: Tytell
authors.forename: M
authors.initials: M
authors.lastname: Cheetham
authors.forename: B
authors.initials: B
authors.lastname: Margulis
mesh_terms: D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D002273:Carcinogens; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D016900:Neurofilament Proteins; D010703:Phorbol Esters; D000255:Adenosine Triphosphate; D019311:Staurosporine