The influence of hyperthermic stress on the redox state of glucocorticoid receptor.
Glucocorticoid receptor (GR) is hormone-dependent transcription factor which participates in intracellular signal transduction. The reduced state of the receptor sulfhydryl groups is considered a necessary prerequisite for its normal functioning under the homeostatic conditions. The aim of the work presented in this paper was to examine the influence of non-homeostatic conditions - whole body hyperthermic stresses at 41 degrees C and 42 degrees C, on GR redox state. Non-reducing SDS-PAGE and immunoblot analysis were used to trace alterations of the receptor's redox state. The steroid binding assay was performed in order to examine direct influence of the whole body heat stresses on the receptor thiols. The results obtained show that the 41 degrees C stress leads to formation of intermolecular disulfide bonds between apo-GR and associated heat shock proteins (Hsp90, Hsp70). Apart from intermolecular GR-Hsp90 and GR-Hsp70 disulfide linkages, 42 degrees C hyperthermic stress also caused creation of intramolecular ones within GR. The results imply malfunctioning of intracellular redox control mechanisms under the hyperthermic conditions.
Department of Biochemistry, Institute for Biological Research, Belgrade, Yugoslavia.
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D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D001831:Body Temperature / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006979:Hyperthermia, Induced; D008099:Liver / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D019810:Sodium Azide / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D013438:Sulfhydryl Compounds; D019810:Sodium Azide; D006861:Hydrogen Peroxide