铁代谢:从炎症到癌症

A. DiPaola, C. Tortora, M. Argenziano, C. DiLeva, F. Rossi
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摘要

铁是几种生理细胞功能所必需的微量元素,其代谢的任何改变都可能与几种疾病的发生有关。细胞通常避免任何失调,激活精细的分子机制来平衡铁的吸收、利用、再循环、储存和输出。在细胞和系统水平上,这一事件的主要“参与者”是hepcidin、铁转运蛋白、铁蛋白和转铁蛋白。铁稳态失调与炎症的发生和延续、骨质疏松和癌症进展密切相关。在炎症期间,已观察到循环铁的减少是铁蛋白水平增加的直接后果,旨在控制炎症过程,并在许多情况下恢复免疫反应。铁超载直接促进骨吸收,抑制骨质形成,诱发骨质疏松。此外,铁细胞积累负责ROS的产生,随之而来的DNA损伤和细胞的肿瘤转化。总之,尽管许多分子机制尚待阐明,但针对铁及其代谢介质可能有助于治疗多种疾病,如炎症、免疫疾病、骨质疏松症和癌症。
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Iron Metabolism: From Inflammation to Cancer
Iron is a trace element essential for several physiological cell functions and any alteration in its metabolism could be associated to the onset of several disorders. Cells normally avoid any dysregulation, activating fine molecular mechanisms to balance iron uptake, utilization, recycling, storage and export. The main “actors” in this event are hepcidin, ferroportin, ferritin and transferrin, both at cell and systemic level. Dysregulation in iron homeostasis is closely related to inflammation onset and perpetuation, osteoporosis and cancer progression. During inflammation, it has been observed a reduction in circulating iron as direct consequence of increase in ferritin levels, aimed to contain inflammatory processes and in many cases to restore the immune response. Iron overload directly promotes bone resorption and inhibits bone formation inducing osteoporosis. Moreover, iron cellular accumulation is responsible for ROS production with consequent DNA damage and neoplastic transformation of cells. In conclusion, even though many molecular mechanisms have to be clarified, targeting iron and also the mediators of its metabolism could be useful to manage a great variety of disorders, such inflammation, immune diseases, osteoporosis and cancer.
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