Ca(2+)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids.
A calcium and NAD(P)H-dependent H(2)O(2)-generating activity has been studied in paranodular thyroid tissues from four patients with cold thyroid nodules and from nine diffuse toxic goiters. H(2)O(2) generation was detected both in the particulate (P 3,000 g) and in the microsomal (P 100,000 g) fractions of paranodular tissue surrounding cold thyroid nodules (PN), with the same biochemical properties described for NADPH oxidase found in porcine and human thyroids. In PN tissues, the particulate NADPH oxidase activity (224 +/- 38 nmol H(2)O(2) x h(-1) x mg(-1) protein) was similar to that described for the porcine thyroid enzyme. However, no NADPH oxidase activity was detectable in the particulate fractions from eight diffuse toxic goiter patients treated with iodine before surgery; all but one also received propylthiouracil or methimazole in the preoperative period. Thyroid cytochrome c reductase (diffuse toxic goiters = 438 +/- 104 nmol NADP(+) x h(-1) x mg(-1) protein; PN = 78 +/- 10 nmol NADP(+) x h(-1) x mg(-1) protein) and thyroperoxidase (diffuse toxic goiters = 621 +/- 179 U x g(-1) protein; PN = 232 +/- 121 U x g(-1) protein) activities were unaffected by iodide. Thus, the human NADPH oxidase seems to be inhibited by iodinated compounds in vivo and probably is an enzyme involved in the Wolff-Chaikoff effect. Our findings reinforce the hypothesis that thyroid NADPH oxidase is responsible for the production of H(2)O(2) necessary for thyroid hormone biosynthesis.
Cardoso
L C
LC
Instituto de Biofísica Carlos Chagas Filho, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
Martins
D C
DC
Figueiredo
M D
MD
Rosenthal
D
D
Vaisman
M
M
Violante
A H
AH
Carvalho
D P
DP
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007454:Iodides / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood
D006728:Hormones; D007454:Iodides; D013963:Thyroid Hormones; D009249:NADP; D006861:Hydrogen Peroxide; D009251:NADPH-Ferrihemoprotein Reductase; D019255:NADPH Oxidases; D002118:Calcium