Human copper transporters: mechanism, role in human diseases and therapeutic potential.
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.
Gupta
Arnab
A
Department of Physiology, Johns Hopkins University, Baltimore, MD 21205, USA.
Lutsenko
Svetlana
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011487:Protein Conformation
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D002945:Cisplatin
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