title: Negative correlation between thyroperoxidase and dual oxidase H2O2-generating activities in thyroid nodular lesions.
abstract: Iodine incorporation into thyroglobulin is dependent on the activities of both thyroperoxidase (TPO) and thyroid dual oxidase 2 (DuOx2). Although TPO expression is decreased in some thyroid nodular lesions, DuOx1 and 2 mRNA expressions are maintained, but DuOx H2O2-generating activity has never been evaluated in such tumors. Our goal was to determine DuOx activity in hypofunctioning lesions of the thyroid. We evaluated H2O2 generation by DuOx in 12 paranodular to cold nodule samples, 17 non-toxic multinodular goiters (MNG; 33 samples), 3 papillary carcinomas (PC; 4 samples), 3 follicular carcinomas (FC; 4 samples), and 10 follicular adenomas. DuOx activity was detected in all paranodular tissues (121+/-23 nmol H2O2/h per mg protein), but was undetectable (<1 nmol H2O2 generated) in all PC, two out of four FC samples and seven out of ten adenomas. In 11 MNG at least two different areas of the goiter have been evaluated, and in 5 of these goiters one of the samples had DuOx activity below the limit of detection. The coefficient of variation in MNG samples ranged from 11.3 to 57.2%. Interestingly, in all the adenomas studied, TPO activity (486+/-142 U/g protein, n=8) was well within the range found in paranodular tissues (414+/-116 U/g protein, n=3). We found a significant negative correlation between DuOx and TPO activities, suggesting that these enzymes are regulated in opposite directions, at least in thyroid tumors.
authors.affiliation: Laboratório de Fisiologia Endócrina Doris Rosenthal from Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21949-900, Brasil.
authors.forename: Maria Gloria P
authors.initials: MG
authors.lastname: Ginabreda
authors.forename: Luciene C
authors.initials: LC
authors.lastname: Cardoso
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Nobrega
authors.forename: Andrea C F
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Manuel Domingos C
authors.initials: MD
authors.lastname: Gonçalves
authors.forename: Mário
authors.initials: M
authors.lastname: Vaisman
authors.forename: Denise P
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000378:metabolism; D000236:Adenoma / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism; D000074623:Dual Oxidases; D005260:Female; D005420:Flavoproteins / Q000378:metabolism*; D006042:Goiter / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism; D016606:Thyroid Nodule / Q000201:enzymology / Q000378:metabolism*
chemical_list: D005420:Flavoproteins; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431515:DUOX2 protein, human