Propylthiouracil, Perchlorate, and Thyroid-Stimulating Hormone Modulate High Concentrations of Iodide Instigated Mitochondrial Superoxide Production in the Thyroids of Metallothionein I/II Knockout Mice

Qi Duan; Tingting Wang; Na Zhang; Vern Perera; Xue Liang; Iruni Roshanie Abeysekera; Xiaomei Yao

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자료유형: 학술저널

저자정보: Qi Duan (Tianjin Medical University) Tingting Wang (Tianjin Medical University) Na Zhang (Tianjin Medical University) Vern Perera (Tianjin Medical University) Xue Liang (Tianjin Medical University) Iruni Roshanie Abeysekera (Tianjin Medical University) Xiaomei Yao (Tianjin Medical University)

저널정보: 대한내분비학회 Endocrinology and Metabolism Endocrinology and Metabolism Vol.31 No.1

발행연도: 2016.1

수록면: 174 - 184 (11page)

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Background: Increased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thy roid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO4), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentra tions of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice. Methods: Eight-week-old 129S7/SvEvBrd-Mt1 tm1Bri Mt2tm1Bri/J (MT-I/II KO) mice and background-matched wild type (WT) mice were used. Results: By using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thia zolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochon drial superoxide production induced by potassium iodide (100 μM) can be relieved by 300 μM PTU, 30 μM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant de crease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were de tected in MT-I/II KO mice (P<0.05). Conclusion: We concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of io dide-induced mitochondrial superoxide production in the thyroid.

참고문헌 (61)

참고문헌 신청

Corvilain B / 2000 / Stimulation by iodide of H2O2 generation in thyroid slices from several species / Am J Physiol Endocrinol Metab 278:E692~E699

Bürgi H / 2010 / Iodine excess / Best Pract Res Clin Endocrinol Metab 24:107~115

Poncin S / 2008 / Oxidative stress in the thyroid gland : from harmlessness to hazard depending on the iodine content / Endocrinology 149:424~433

Chiaverini N / 2010 / Protective effect of metallothionein on oxidative stress-induced DNA damage / Free Radic Res 44:605~613

Miles AT / 2000 / Induction, regulation, degradation, and biological significance of mammalian metallothioneins / Crit Rev Biochem Mol Biol 35:35~70

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