Zinc ions antagonize the inhibitory effect of aurothiomalate on glucocorticoid receptor function at physiological concentrations

Hirotoshi Tanaka, Yuichi Makino, Karin Dahlman Wright, Jan Åke Gustafsson, Kensaku Okamoto, Isao Makino

    Research output: Contribution to journalArticlepeer-review

    7 Scopus citations

    Abstract

    The water-soluble gold preparation aurothiomalate, which contains gold as Au(I), is frequently prescribed for patients with rheumatoid arthritis as a disease-modifying agent. We report that aurothiomalate negatively modulates glucocorticoid hormone action; it represses the ligand- and DNA-binding activities; and the transactivation function of the glucocorticoid receptor. We suggested the existence of endogenous titrating activities of Au(I) because otherwise administration of aurothiomalate to a patient with rheumatoid arthritis would be expected to result in peripheral insensitivity to glucocorticoids and worsen the patient's status. Focusing on metal ions that are present in vivo, we found that Zn(II) counteracts the inhibitory effect of Au(I) on glucocorticoid receptor function. This complementary effect of Zn(II) was observed at physiological concentrations. We suggest that Zn(II) preserves glucocorticoid receptor function in target tissues and maintains hormone responsiveness, even with chrysotherapy.

    Original languageEnglish (US)
    Pages (from-to)938-945
    Number of pages8
    JournalMolecular Pharmacology
    Volume48
    Issue number5
    StatePublished - Nov 1995

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

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