Dual oxidase, hydrogen peroxide and thyroid diseases.
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.
Ohye
Hidemi
H
Endocrinology and Diabetes Division, Greater Los Angeles Veterans Affair Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA.
Sugawara
Masahiro
M
D002462:Cell Membrane / Q000378:metabolism; D000074623:Dual Oxidases; D015971:Gene Expression Regulation, Enzymologic; D050031:Hashimoto Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013959:Thyroid Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D014018:Tissue Distribution
D007527:Isoenzymes; D016877:Oxidants; D017382:Reactive Oxygen Species; D013963:Thyroid Hormones; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; C431515:DUOX2 protein, human