鉴定iodotyrosines作为甲状腺激素载体MCT8的新基质
Stefan Groeneweg1,2, Chantal Zevenbergen1,2, Elaine C Lima de Souza1,2
1Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
单碳酸盐输送体8 (MCT8) 输出像DIT和MIT这样的铁素,影响甲状腺激素的输送. 这一发现可能解释了与MCT8缺乏相关的严重残疾.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 代谢学 代谢学 代谢学
背景情况:
- 单碳酸盐运输体8 (MCT8) 对于甲状腺激素运输至关重要.
- 缺少MCT8会导致严重的智力和运动残疾.
- 除了甲状腺激素之外,MCT8的基质特异性在很大程度上是未知的.
研究的目的:
- 为了确定MCT8.8运输的额外基板.
- 研究MCT8基质与甲状腺激素运输之间的相互作用.
- 探索这些相互作用在MCT8缺陷表型中的作用.
主要方法:
- 在Xenopus卵细胞中基于液态染色学和质谱学的代谢组分析.
- 使用[125I]-DIT,[125I]-MIT, [3H]-谷氨酸和 [3H]-谷氨酸在转染的COS-1细胞和人类纤维细胞中的运输研究.
- 使用甲状腺激素 (T3,T4) 和一种MCT8特异性抑制剂 (西利克里斯) 的抑制研究.
主要成果:
- 过度表达MCT8的卵细胞显示出87种代谢物的差异丰富性,包括3,5-二二氨酸 (DIT).
- 表达MCT8的细胞显示[125I]-DIT和[125I]-3-单一离子氨酸 (MIT) 的细胞内积累减少.
- DIT和MIT干扰了MCT8介导的甲状腺激素输送,反之亦然.
结论:
- MCT8的出口是 DIT 和 MIT 的约多提罗辛.
- 由MCT8运输的约多氨酸会影响甲状腺激素的运输.
- 需要进一步的研究来确认MCT8在甲状腺毛囊细胞中的iodotyrosine体内运输.
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