Generation of oxygen free radicals in thyroid cells and inhibition of thyroid peroxidase

Masahiro Sugawara, Yoshinobu Sugawara, Katherine Wen, Cecilia R Giulivi

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We examined whether superoxide (O2 -) is produced as a precursor of hydrogen peroxide (H2O2) in cultured thyroid cells using the cytochrome c method and the electron paramagnetic resonance (EPR) method. No O2 - or its related radicals was detected in thyroid cells under the physiological condition. The presence of quinone, 2,3-dimethoxy-l-naphthoquinone (DMNQ), or 2-methyl-1, 4-naphthoquinone (menadione), in the medium produced O2 - and hydroxyl radicals (OH.); the amount of H2O2 generation was also increased. Incubation of follicles with DMNQ or menadione inhibited iodine organification (a step of thyroid hormone formation) and its catalytic enzyme, thyroid peroxidase (TPO). This inhibition should be caused by reactive oxygen species because the two quinones, particularly DMNQ, exert their effect through the generation of reactive oxygen species. It is speculated that the site-specific inactivation of TPO might have occurred at the heme-linked histidine residue of the TPO molecule, a critical amino acid for enzyme activity because OH. (vicious free radicals) can be formed at the iron-linked amino acid. TPO mRNA level and electrophoretic mobility of TPO were not inhibited by quinones. Our study suggests that thyroid H2O2 is produced by divalent reduction of oxygen without O2 - generation. If thyroid cells happen to be exposed to significant amount of reactive oxygen species, TPO and subsequent thyroid hormone formation are inhibited.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalExperimental Biology and Medicine
Volume227
Issue number2
StatePublished - Feb 2002
Externally publishedYes

Keywords

  • Hydrogen peroxide
  • Quinones
  • Superoxide
  • Thyroid cells
  • Thyroid peroxidase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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