Interaction of rat renal glucocorticoid receptor with Hsp90 and Hsp70 upon stress provoked by mercury

Abstract

The influence of mercury on the association of rat kidney glucocorticoid receptor (GR) with heat shock proteins Hsp90 and Hsp70 was investigated. The GR heterocomplexes with Hsp90 and Hsp70 were immunopurified from the renal cytosol of rats administered different doses of mercury (1, 2 and 3 mg Hg kg(-1) b.w.). A quantitative immunoblotting procedure was applied to determine the levels of GR, Hsp90 and two nucleocytoplasmic Hsp70 isoforms (constitutive Hsp73 and inducible Hsp72) in the renal cytosol, as well as the amounts of these proteins within GR heterocomplexes immunoprecipitated by anti-GR antibody. Mercury was found to stimulate GR association with all the examined Hsps. The most prominent effect of the metal was stimulation of Hsp72 interaction with GR. On the other hand, the metal administration led to an increase of Hsp90 level in the cytosol, while the cytosolic levels of Hsp70 isoforms remained unaltered. These findings suggest that association of Hsps, at least Hsp70, with the GR might be ascribed to changes in the affinity of their interaction rather than to changes in the Hsp availability in the cytosol. Therefore, GR heterocomplex assembly seems to be a controlled process enabling chaperoning and functioning of the GR to be in concert with physiological demands.

Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome

“…Although the lymphocyte Hsp90 and Hsp70 concentrations were not changed in the studied women with PCOS in comparison to the controls, a possibility of altered GR/Hsp90 and/or GR/Hsp70 interaction can not be ruled out. Namely, these interactions do not depend solely on the intracellular concentrations of the chaperones, but rely on the mechanisms regulating the assembly of the receptor heteromultimeric complexes ( Brkljačić et al, 2007 ), as well. In the present study, the only diff erence between obese women with PCOS and their normal-weight counterparts appeared to be a weaker correlation between B max and K D in the obese group.…”

Immunology of Mercury

“…Although the cellular mechanisms allowing such crisscross pathways are not clear, chaperones such as heat shock proteins might mediate both cross‐presentation pathways for exogenous antigens on MHC class I molecules, and for endogenous antigens on MHC class II molecules 140,141 . Interestingly, mercury increases the levels of both cytoplasmic and nucleocytoplasmic heat shock proteins, 142–145 allowing for the possibility that in mercury‐treated cells, alternately processed or mercury‐modified fibrillarin epitopes are presented by MHC class II molecules to CD4 T cells, breaking T cell tolerance to this self protein.…”

Physiological Condition of Juvenile Wading Birds in Relation to Multiple Landscape Stressors in the Florida Everglades: Effects of Hydrology, Prey Availability, and Mercury Bioaccumulation

“…Up-regulation of heat shock proteins are associated with protective stress responses to minimize cell protein damage [40], [41], [64]. Methylmercury exposure in birds is associated with oxidative stress in liver, kidney, and brain tissue [65], and up-regulation of heat shock proteins has recently been identified as a potential biological defense mechanism against MeHg toxicity [66], [67]. However, it is unclear what the consequences are for down-regulation of heat shock proteins as we observed with egrets.…”