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Title 

Methimazole as an antioxidant and immunomodulator in thyroid cells : mechanisms involving interferon-γ signaling and H2O2 scavenging

Authors 

Ho KimTae Hoon LeeYoung Sun HwangMi Ae BangKang Hwa KimJae Mi SuhHyo Kyun ChungDae Yeul YuKyung Kwang LeeO Yu KwonHong Kyu RoMin Ho Shong

Publisher 

American Society for Pharmacology and Experimental Therapeutics (ASPET)

Issue Date 

2001

Citation 

Molecular Pharmacology, vol. 60, no. 5, pp. 972-980

Keywords 

antioxidantgamma interferonintercellular adhesion molecule 1animal cellantioxidant activitydrug mechanismthyroid cellantioxidantscells, culturedintercellular adhesion molecule-1

Abstract 

The antithyroid drug, methimazole (MMI) is used to treat patients with Graves' hyperthyroidism. The major action of MMI is to inhibit synthesis of thyroid hormone in the thyroid gland. However, MMI also has antioxidant and immunomodulatory effects on thyrocytes and/or immune cells. This study identifies novel antioxidant and immunomodulatory effects of MMI involving the interferon-γ (IFN-γ) signaling pathway in thyroid cells. MMI inhibits transcription of the intercellular adhesion molecule-1 (ICAM-1) gene by modulating the function of transcription factor STAT1 (signal transducer and activator of transcription 1), which binds to the IFN-γ activated site of the ICAM-1 promoter. Furthermore, MMI rapidly eliminates H2O2 produced by IFN-γ treatment in thyroid cells and thus inhibits the H2O2-mediated phosphorylation of tyrosine 701 in STAT1. MMI also eliminates H2O2 in vitro. MMI facilitates electron transfer from NADPH to H2O2 using thioredoxin or glutathione, fulfilling a role similar to peroxiredoxin or glutathione peroxidase, respectively. MMI prevents the IFN-γ and H2O2-mediated reversible inactivation of phosphatases. These effects inhibit full activation of the IFN-γ-induced Janus kinase(JAK)/STAT signaling pathway in FRTL-5 thyroid cells. These results may in part explain the antioxidant and immunomodulatory effects of MMI in thyroid cells of Graves' disease patients.

ISSN 

0026-895X

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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