title: Amyloid-β(25-35) induces a permanent phosphorylation of HSF-1, but a transitory and inflammation-independent overexpression of Hsp-70 in C6 astrocytoma cells.
abstract: Two hallmarks of Alzheimer diseases are the continuous inflammatory process, and the brain deposit of Amyloid b (Aβ), a cytotoxic protein. The intracellular accumulation of Aβ(25-35) fractions, in the absence of Heat Shock proteins (Hsṕs), could be responsible for its cytotoxic activity. As, pro-inflammatory mediators and nitric oxide control the expression of Hsṕs, our aim was to investigate the effect of Aβ(25-35) on the concentration of IL-1β, TNF-α and nitrite levels, and their relation to pHSF-1, Hsp-60, -70 and -90 expressions, in the rat C6 astrocyte cells. Interleukin-specific ELISA kits, immunohistochemistry with monoclonal anti-Hsp and anti pHSF-1 antibodies, and histochemistry techniques, were used. Our results showed that Aβ25-35 treatment of C6 cells increased, significantly and consistently the concentration of IL-1β, TNF-α and nitrite 3 days after initiating treatment. The immunoreactivity of C6 cells to Hsp-70 reached its peak after 3 days of treatment followed by an abrupt decrease, as opposed to Hsp-60 and -90 expressions that showed an initial and progressive increase after 3 days of Aβ(25-35) treatment. pHSF-1 was identified throughout the experimental period. Nevertheless, progressive and sustained cell death was observed during all the treatment times and it was not caspase-3 dependent. Our results suggest that Hsp-70 temporary expression serves as a trigger to inhibit casapase-3 pathway and allow the expression of Hsp-60 and -90 in C6 astrocytoma cells stimulated with Aβ(25-35).
authors.affiliation: Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía "MVS", Mexico D.F. 14059, Mexico.
authors.forename: Minerva
authors.initials: M
authors.lastname: Calvillo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Diaz
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Limon
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Mayoral
authors.forename: María Elena
authors.initials: ME
authors.lastname: Chánez-Cárdenas
authors.forename: Edgar
authors.initials: E
authors.lastname: Zenteno
authors.forename: Luis F
authors.initials: LF
authors.lastname: Montaño
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinosa
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001254:Astrocytoma; D016923:Cell Death; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D007249:Inflammation / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D010446:Peptide Fragments; D014157:Transcription Factors; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide
keywords: Alzheimeŕs disease; C6 glioma cells; Heat shock proteins; Inflammatory cytokines; Nitric oxide