title: Inhibition of thyroid NADPH-oxidase by 2-iodohexadecanal in a cell-free system.
abstract: The major nonpolar iodolipid formed in horse thyroid cells has recently been identified as 2-iodohexadecanal (2-IHDA). We have investigated in vitro the effect of 2-IHDA on the NADPH-oxidase, NADPH-cytochrome c reductase, and thyroid peroxidase (TPO) activities of a porcine thyroid plasma membrane preparation. 2-IHDA inhibited NADPH-oxidase activity, with half-inhibition at 3-5 microM, but it had no effect on NADPH-cytochrome c reductase. It inhibited the TPO-catalyzed iodination of protein, but not iodide oxidation. Hexadecanal also inhibited NADPH-oxidase. Inhibition by the non-iodinated lipid aldehydes depended on the length of their aliphatic chain: dodecanal and tridecanal gave maximal inhibition. Free iodide, 2-iodohexadecanol and palmitic acid all had no inhibitory effect. Washing treated membranes showed that the inhibition of NADPH-oxidase by hexadecanal was fully reversible, whereas that of 2-IHDA and other iodinated or brominated alkanals was irreversible. Thus the interaction between some residues of the thyroid NADPH-oxidase and the lipid aldehyde groups was favored or stabilized by the iodine atom. Modification of primary amine and thiol groups of NADPH-oxidase inhibited its activity. These groups could also be the target of lipid aldehydes. We suggest that 2-IHDA, because it inhibits TPO and more profoundly the H2O2-generating system in thyroid plasma membrane, modulates iodide metabolism in the thyrocyte and may mediate the Wolff-Chaikoff effect.
authors.affiliation: Unité 96 INSERM, Le Kremlin-Bicêtre, France.
authors.forename: R
authors.initials: R
authors.lastname: Ohayon
authors.forename: J M
authors.initials: JM
authors.lastname: Boeynaems
authors.forename: J C
authors.initials: JC
authors.lastname: Braekman
authors.forename: H
authors.initials: H
authors.lastname: Van den Bergen
authors.forename: Y
authors.initials: Y
authors.lastname: Gorin
authors.forename: A
authors.initials: A
authors.lastname: Virion
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002474:Cell-Free System; D006861:Hydrogen Peroxide / Q000378:metabolism; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors; D007455:Iodine / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D013329:Structure-Activity Relationship; D013552:Swine; D013961:Thyroid Gland / Q000201:enzymology*
chemical_list: D000447:Aldehydes; D008565:Membrane Proteins; C065952:2-iodohexadecanal; D007455:Iodine; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D019255:NADPH Oxidases