Human copper transporters: mechanism, role in human diseases and therapeutic potential.

Human copper transporters: mechanism, role in human diseases and therapeutic potential.
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DOI:
10.4155/fmc.09.84
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发表时间:
2009-09
影响因子:
4.2
通讯作者:
Lutsenko S
Lutsenko S
中科院分区:
医学3区
文献类型:
--
作者:
Gupta A;Lutsenko S

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正常的铜稳态对人类的生长和发育至关重要。铜突变、饮食不足或手术干预可能导致心脏肥大、神经元髓鞘形成不良、血管异常和免疫反应受损。铜超载与组织的形态和代谢变化有关,如果不治疗,最终死亡。最近的报道还表明,铜转运蛋白表达的变化改变了癌细胞对主要化疗药物(如顺铂)的敏感性,尽管这一重要现象背后的机制仍不清楚。本文综述了铜转运蛋白CTR 1、CTR 2、ATP 7A和ATP 7B的分子特征、在哺乳动物体内铜稳态中的作用及其失活的生理后果。铜转运蛋白可能会影响细胞对顺铂的敏感性的机制进行了讨论。调节人体铜稳态具有重要的治疗潜力,需要详细了解铜转运机制。
Normal copper homeostasis is essential for human growth and development. Copper mutations, inadequate diet or surgical interventions, may lead to cardiac hypertrophy, poor neuronal myelination, blood vessel abnormalities and impaired immune response. Copper overload is associated with morphological and metabolic changes in tissues and, if untreated, eventual death. Recent reports also indicate that changes in the expression of copper transporters alter the sensitivity of cancer cells to major chemotherapeutic drugs, such as cisplatin, although the mechanism behind this important phenomenon remains unclear. This review summarizes current information on the molecular characteristics of copper transporters CTR1, CTR2, ATP7A and ATP7B, their roles in mammalian copper homeostasis and the physiological consequences of their inactivation. The mechanisms through which copper transporters may influence cell sensitivity to cisplatin are discussed. Regulation of human copper homeostasis has significant therapeutic potential and requires the detailed understanding of copper transport mechanisms.
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