Dual oxidase, hydrogen peroxide and thyroid diseases

Exp Biol Med (Maywood). 2010 Apr;235(4):424-33. doi: 10.1258/ebm.2009.009241.

Abstract

The thyroid gland is a unique endocrine organ that requires hydrogen peroxide (H(2)O(2)) for thyroid hormone formation. The molecule for H(2)O(2) production in the thyroid gland has been known as dual oxidase 2 (DUOX2). Recently, NADPH oxidase 4 (NOX4), a homolog of the NOX family, was added as a new intracellular source of reactive oxygen species (ROS) in the human thyroid gland. This review focuses on the recent progress of the DUOX system and its possible contribution to human thyroid diseases. Also, we discuss human thyroid diseases related to abnormal H(2)O(2) generation. The DUOX molecule contains peroxidase-like and NADPH oxidase-like domains. Human thyroid gland also contains DUOX1 that shares 83% similarity with the DUOX2 gene. However, thyroid DUOX1 protein appears to play a minor role in H(2)O(2) production. DUOX proteins require DUOX maturation or activation factors (DUOXA1 or 2) for proper translocation of DUOX from the endoplasmic reticulum to the apical plasma membrane, where H(2)O(2) production takes place. Thyroid cells contain antioxidants to protect cells from the H(2)O(2)-mediated oxidative damage. Loss of this balance may result in thyroid cell dysfunction and thyroid diseases. Mutation of either DUOX2 or DUOXA2 gene is a newly recognized cause of hypothyroidism due to insufficient H(2)O(2) production. Papillary thyroid carcinoma, the most common thyroid cancer, is closely linked to the increased ROS production by NOX4. Hashimoto's thyroiditis, a common autoimmune thyroid disease in women, becomes conspicuous when iodide intake increases. This phenomenon may be explained by the abnormality of iodide-induced H(2)O(2) or other ROS in susceptible individuals. Discovery of DUOX proteins and NOX4 provides us with valuable tools for a better understanding of pathophysiology of prevalent thyroid diseases.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cell Membrane / metabolism
  • Dual Oxidases
  • Gene Expression Regulation, Enzymologic
  • Hashimoto Disease / metabolism
  • Hashimoto Disease / pathology
  • Hashimoto Disease / physiopathology
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Hypothyroidism / genetics
  • Hypothyroidism / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Oxidants / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Thyroid Diseases* / metabolism
  • Thyroid Diseases* / pathology
  • Thyroid Diseases* / physiopathology
  • Thyroid Gland / metabolism*
  • Thyroid Hormones / metabolism
  • Tissue Distribution

Substances

  • Isoenzymes
  • Oxidants
  • Reactive Oxygen Species
  • Thyroid Hormones
  • Hydrogen Peroxide
  • Dual Oxidases
  • NADPH Oxidases
  • DUOX1 protein, human
  • DUOX2 protein, human