Effect of oxidative stress on rat thyrocyte iodide metabolism.
Thyroid cells fall into the type of cells functioning during continuous production of high H(2)O(2) concentrations. We studied the effect of H(2)O(2)-induced oxidative stress (0.1, 1.0 and 10.0 mM) on the activities of the key steps of iodide metabolism (uptake, oxidation and organification) in thyrocytes cultivated in an organ culture. After 60 min cultivation of cells in a medium containing H(2)O(2) at concentrations of 1.0 and 10.0 mM iodide (I(-)) uptake, thyroperoxidase (TPO) activity and I(-) organification were completely inhibited. No restoration of the parameters studied was observed within the subsequent 24 h of cultivation. The inhibitory effect of 0.1 mM H(2)O(2) was reversible. Activation of I(-) uptake in the cultivated tissue and a 520-880% increase of the total I(-) content were observed after 8 and 24 h. The concentration of I(-) protein-bound fraction was raised by 220% after 24 h. A biphasic effect of 0.1 mM H(2)O(2) on TPO was observed: 76.2% and 72.2% inhibitions were seen after 2 and 8 h, respectively, whereas 40.0% enzyme activation was after 5 h. TPO activity was partially restored after 24 h and amounted to 65% of the initial value. The significant increase in the concentration of iodide protein-bound fraction, which was observed simultaneously with TPO inhibition, could be due to thyroglobulin non-enzymic iodination under H(2)O(2)-generated oxidative stress. The data obtained indicate that iodide oxidation, as a step in the biosynthesis of thyroid hormones, was most sensitive to oxidative stress activation. The impaired iodide uptake and its organification during oxidative stress can play a pathogenetic role in disturbed functions of thyroid cells.
Institute of Pharmacology and Biochemistry of the National Academy of Sciences of Belarus, Belarus. lnadolnik@tut.by
L I
LI
Nadolnik
Z V
ZV
Niatsetskaya
S V
SV
Lupachyk
D000818:Animals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000378:metabolism; D007454:Iodides / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D007454:Iodides; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase