Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells.

Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells.
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抑制镉抗性金属硫蛋白缺失细胞中锰的高亲和力转运系统。

DOI:
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发表时间:
2000
影响因子:
3.5
通讯作者:
S. Himeno
S. Himeno
中科院分区:
医学2区
文献类型:
--
作者:
T. Yanagiya;N. Imura;S. Enomoto;Y. Kondo;S. Himeno

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镉是一种普遍存在于环境中的有害重金属,但镉进入哺乳动物细胞的机制一直知之甚少。最近,我们从永生化的金属硫蛋白缺失的小鼠细胞中建立了耐镉细胞系(Cd-Rb5),发现Cd-Rb5细胞对镉的摄取明显减少。为了研究Cd-Rb5细胞对镉摄取改变的机制,用多示踪技术同时测定了多种金属的掺入。Cd-Rb5细胞的锰掺入明显减少,镉的掺入也明显减少。然而,只有在低浓度时才能观察到对锰的摄取减少,这表明在CD-Rb5细胞中,锰(2+)转运系统的一个高亲和力成分受到抑制。竞争实验和动力学分析表明,低浓度的Cd(2+)和Mn(2+)具有相同的高亲和力进入细胞的途径。HeLa、PC12和Caco-2细胞对Cd(2+)和Mn(2+)的摄取也存在相互竞争。亲本细胞对Cd(2+)和Mn(2+)的吸收在中性条件下最高,这表明这一途径不同于在酸性条件下可以运输包括Cd(2+)和Mn(2+)在内的各种二价金属的二价金属转运体1。这些结果表明,高亲和力的Mn(2+)转运系统被用于哺乳动物细胞对镉的摄取,并且抑制这一途径导致耐镉金属硫蛋白缺失细胞中镉的积累显著减少。
Cadmium is a hazardous heavy metal existing ubiquitously in the environment, but the mechanism of cadmium transport into mammalian cells has been poorly understood. Recently, we have established a cadmium-resistant cell line (Cd-rB5) from immortalized metallothionein-null mouse cells, and found that Cd-rB5 cells exhibited a marked decrease in cadmium uptake. To investigate the mechanism of altered uptake of cadmium in Cd-rB5 cells, incorporation of various metals was determined simultaneously using a multitracer technique. Cd-rB5 cells exhibited a marked decrease in manganese incorporation as well as that of cadmium. However, the reduced uptake of manganese was observed only at low concentrations, suggesting that a high-affinity component of the Mn(2+) transport system was suppressed in Cd-rB5 cells. Competition experiments and kinetic analyses revealed that low concentrations of Cd(2+) and Mn(2+) share the same high-affinity pathway for their entry into cells. The mutual competition of Cd(2+) and Mn(2+) uptake was also observed in HeLa, PC12, and Caco-2 cells. The highest uptake of Cd(2+) and Mn(2+) by parental cells occurred at neutral pH, suggesting that this pathway is different from a divalent metal transporter 1 that can transport various divalent metals including Cd(2+) and Mn(2+) under acidic conditions. These results suggest that a high-affinity Mn(2+) transport system is used for mammalian cellular cadmium uptake, and that the suppression of this pathway caused a marked decrease in cadmium accumulation in cadmium-resistant metallothionein-null cells.
金属离子与镉诱导的细胞毒性的相互作用。
DOI: 10.1080/15287398109529966
发表时间: 1981
期刊: Journal of toxicology and environmental health
影响因子: --
作者:
Stacey,NH;Klaassen,CD
通讯作者: Klaassen,CD
DOI: 10.1016/0006-2952(85)90673-2
发表时间: 1985
影响因子: 5.8
作者:
Goering,PL;Klaassen,CD
通讯作者: Klaassen,CD
DOI: 10.1073/pnas.90.17.8088
发表时间: 1993-09-01
影响因子: 11.1
作者:
MICHALSKA, AE;CHOO, KHA
通讯作者: CHOO, KHA
DOI: 10.1016/0300-483x(85)90118-0
发表时间: 1985-01-01
期刊: TOXICOLOGY
影响因子: 4.5
作者:
FOULKES, EC
通讯作者: FOULKES, EC
DOI: 10.1016/s0021-9258(18)49259-9
发表时间: 1987-12
期刊: The Journal of biological chemistry
影响因子: --
作者:
Patricia;Hinkle;Kinsella;K. Osterhoudt
通讯作者: Patricia;Hinkle;Kinsella;K. Osterhoudt