The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase
The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase
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DOI：
10.1073/pnas.95.7.3483
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Vallee, BL
中科院分区：
文献类型：
--
作者：
Jiang, LJ;Maret, W;Vallee, BL
利用锌从金属硫蛋白(MT)到缺锌山梨醇脱氢酶(EC 1.1.1.14)的体外释放和转移来探讨MT在细胞锌分布中的作用，MT和山梨醇脱氢酶的摩尔比需要1：1才能完全重新激活，表明在这一过程中MT的7个锌原子中只有一个被转移，还原型谷胱甘肽(GSH)和谷胱甘肽二硫化物(GSSG)是锌转移速率和最终转移锌原子数的关键调节器，GSSG使锌转移速度提高3倍，其浓度是锌转移效率的主要决定因素。GSH具有双重功能，在没有GSSG的情况下，它抑制MT的锌转移，表明MT在相对较高的细胞浓度下处于潜伏状态，此外，它通过提高锌转移速度10倍和通过增加转移到四个锌原子的数目来启动MT与GSSG的反应。锌-65标记实验证实，在没有谷胱甘肽的情况下，MT释放一个锌，而在GSH和GSSG存在的情况下，MT更有效地释放锌。在体外，MT可能使细胞内游离锌的浓度保持在很低的水平，并作为细胞的临时储库。锌的释放过程受其与GSH和GSSG相互作用的动态控制，这些结果表明细胞氧化还原状态的改变可能是MT分配锌的驱动力和信号。
The release and transfer of zinc from metallothionein (MT) to zinc-depleted sorbitol dehydrogenase (EC 1.1.1.14) in vitro has been used to explore the role of MT in cellular zinc distribution, A 1:1 molar ratio of MT to sorbitol dehydrogenase is required for full reactivation, indicating that only one of the seven zinc atoms of MT is transferred In this process, Reduced glutathione (GSH) and glutathione disulfide (GSSG) are critical modulators of both the rate of zinc transfer and the ultimate number of zinc atoms transferred, GSSG increases the rate of zinc transfer 3-fold, and its concentration is the major determinant for efficient zinc transfer, GSH has a dual function, In the absence of GSSG, it inhibits zinc transfer from MT, indicating that MT is In a latent state under the relatively high cellular concentrations of GSH, In addition, it primes MT for the reaction with GSSG by enhancing the rate of zinc transfer 10-fold and by increasing the number of zinc atoms transferred to four, Zn-65-labeling experiments confirm the release of one zinc from MT in the absence of glutathione and the more effective release of zinc in the presence of GSH and GSSG, In vitro, MT may keep the cellular concentrations of free zinc very low and, acting as a temporary cellular reservoir, release zinc in a process that is dynamically controlled by its interactions with both GSH and GSSG, These results suggest that a change of the redox state of the cell could serve as a driving force and signal for zinc distribution from MT.