The BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for iodide toxicity in Caenorhabditis elegans.
The BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for iodide toxicity in Caenorhabditis elegans.
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BLI-3/TSP-15/DOXA-1 双氧化酶复合物是秀丽隐杆线虫碘化物毒性所必需的
DOI：
10.1534/g3.114.015982
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发表时间：
2014-12-04
期刊：
影响因子：
--
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Xu Z;Luo J;Li Y;Ma L
碘是生命必需的微量元素。碘缺乏可导致甲状腺激素的生物合成缺陷，是甲状腺功能减退和智力迟钝的主要原因。然而，过量的碘摄入与不同的甲状腺疾病有关。过量的碘是如何引起有害影响的还不清楚。在这里，我们发现，线虫秀丽隐杆线虫表现出发育停滞和其他多效性缺陷时，暴露于过量的碘化物。为了确定相关基因，我们进行了正向遗传筛选，并分离出12个可以在过量碘中存活的突变体。这些突变体定义了至少四个基因，其中两个我们确定为bli-3和tsp-15。bli-3编码C.哺乳动物双氧化酶DUOX 1和tsp-15的线虫直向同源物编码四跨膜蛋白TSP-15，其先前显示与BLI-3相互作用。梭线虫双氧化酶成熟因子DOXA-1也是过量碘化物的抑制作用所必需的。最后，我们检测到在过量碘处理的动物中活性氧的生物合成显著增加，并且这种效应可以被bli-3和tsp-15突变部分抑制。我们认为BLI-3/TSP-15/DOXA-1双氧化酶复合物是过量碘的毒性多效性效应所必需的。
Iodine is an essential trace element for life. Iodide deficiency can lead to defective biosynthesis of thyroid hormones and is a major cause of hypothyroidism and mental retardation. Excess iodide intake, however, has been linked to different thyroidal diseases. How excess iodide causes harmful effects is not well understood. Here, we found that the nematode Caenorhabditis elegans exhibits developmental arrest and other pleiotropic defects when exposed to excess iodide. To identify the responsible genes, we performed a forward genetic screen and isolated 12 mutants that can survive in excess iodide. These mutants define at least four genes, two of which we identified as bli-3 and tsp-15. bli-3 encodes the C. elegans ortholog of the mammalian dual oxidase DUOX1 and tsp-15 encodes the tetraspanin protein TSP-15, which was previously shown to interact with BLI-3. The C. elegans dual oxidase maturation factor DOXA-1 is also required for the arresting effect of excess iodide. Finally, we detected a dramatically increased biogenesis of reactive oxygen species in animals treated with excess iodide, and this effect can be partially suppressed by bli-3 and tsp-15 mutations. We propose that the BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for the toxic pleiotropic effects of excess iodide.
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影响因子：
56.9
作者：
BAGCHI, N;BROWN, TR;SUNDICK, RS
通讯作者：
SUNDICK, RS
DOI：
10.12659/msm.883736
发表时间：
2013-01-14
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Dong W;Zhang H;Zhang P;Li X;He L;Wang Z;Liu Y
通讯作者：
Liu Y
影响因子：
4.8
作者：
Grasberger, Helmut;Refetoff, Samuel
通讯作者：
Refetoff, Samuel
影响因子：
2.7
作者：
HIRSH, D;OPPENHEIM, D;KLASS, M
通讯作者：
KLASS, M
影响因子：
15.3
作者：
Klebanoff, S J
通讯作者：
Klebanoff, S J