Department of Physiology, Johns Hopkins University, Baltimore, MD 21205, USA.
Future Med Chem. 2009 Sep;1(6):1125-42. doi: 10.4155/fmc.09.84.
Normal copper homeostasis is essential for human growth and development. Copper deficiency, caused by genetic 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.
正常的铜稳态对人类的生长和发育至关重要。由于基因突变、饮食不足或手术干预等原因导致的铜缺乏，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。铜过载与组织的形态和代谢变化有关，如果不加以治疗，最终会导致死亡。最近的报告还表明，铜转运蛋白表达的变化改变了癌细胞对顺铂等主要化疗药物的敏感性，尽管这一重要现象背后的机制尚不清楚。本综述总结了铜转运蛋白 CTR1、CTR2、ATP7A 和 ATP7B 的分子特征、它们在哺乳动物铜稳态中的作用以及它们失活的生理后果的最新信息。讨论了铜转运蛋白可能影响细胞对顺铂敏感性的机制。人类铜稳态的调节具有重要的治疗潜力，需要详细了解铜转运机制。
