Aluminum fluoride inhibition of glucocorticoid receptor inactivation and transformation

Journal Article · Tue Apr 10 00:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00466a022· OSTI ID:6693722

Housley, P R ^[1]

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1. Univ. of South Carolina School of Medicine, Columbia (USA)

Fluoride, in the presence of aluminum ions, reversibly inhibits the temperature-mediated inactivation of unoccupied glucocorticoid receptors in cytosol preparations from mouse L cells. The effect is concentration-dependent, with virtually complete stabilization of specific glucocorticoid-binding capacity at 2 mM fluoride and 100 microM aluminum. These concentrations of aluminum and fluoride are ineffective when used separately. Aluminum fluoride also stabilizes receptors toward inactivation by gel filtration and ammonium sulfate precipitation. Aluminum fluoride prevents temperature-dependent transformation of steroid-receptor complexes to the DNA-binding state. Aluminum fluoride does not inhibit calf intestine alkaline phosphatase, and unoccupied receptors inactivated by this enzyme in the presence of aluminum fluoride can be completely reactivated by dithiothreitol. The effects of aluminum fluoride are due to stabilization of the complex between the glucocorticoid receptor and the 90-kDa mammalian heat-shock protein hsp90, which suggests that aluminum fluoride interacts directly with the receptor. Endogenous thermal inactivation of receptors in cytosol is not accompanied by receptor dephosphorylation. However, inactivation is correlated with dissociation of hsp90 from the unoccupied receptor. These results support the proposal that hsp90 is required for the receptor to bind steroid and dissociation of hsp90 is sufficient to inactivate the unoccupied receptor.

• OSTI ID: 6693722
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:14; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL HORMONES
ALUMINIUM COMPOUNDS
ALUMINIUM FLUORIDES
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CHROMATOGRAPHY
CORTICOSTEROIDS
FLUORIDES
FLUORINE COMPOUNDS
GLUCOCORTICOIDS
HALIDES
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
KETONES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MICE
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PREGNANES
PROTEINS
REACTION KINETICS
RECEPTORS
RODENTS
SEPARATION PROCESSES
STEROIDS
THERMODYNAMICS
VERTEBRATES