Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.
Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis.
Laboratory of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str, Goudi, GR 11527 Athens, Greece.
E S
ES
Bei
V
V
Salpeas
B
B
Alevizos
C
C
Anagnostara
D
D
Pappa
P
P
Moutsatsou
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; C102948:HSF4 protein, human; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D006854:Hydrocortisone
Bipolar disorder; Glucocorticoid receptor; HSP70-glucocorticoid receptor heterocomplex; HSP90-glucocorticoid receptor heterocomplex; Heat shock factors (HSF1, HSF4); Heat shock proteins (70 kDa, 90 kDa)