哺乳动物 ATP 结合盒转运体的镉转运。

IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Frank Thévenod, Wing-Kee Lee
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引用次数: 0

摘要

细胞对有毒金属的反应取决于金属进入细胞内靶点、到达相互作用位点以及细胞内金属浓度,而细胞内金属浓度主要由吸收途径、结合/螯合途径和外流途径决定。ATP 结合盒(ABC)转运体在人体内无处不在,通常存在于上皮细胞中,负责转运不可或缺的生理底物(如脂质和血红素)、防止潜在的有毒物质、维持体液成分和排泄代谢废物。ABC 转运体的调控失灵和基因变异最终导致一系列病理生理疾病,如肿瘤性多药耐药性或囊性纤维化。镉(Cd)在哺乳动物体内没有已知的生理作用,但由于工业活动将其释放到环境中,并最终进入食物链,因此对健康构成威胁。上皮细胞,尤其是肝脏、肺部、胃肠道和肾脏中的上皮细胞,特别容易受到镉的多方面影响,因为它们有大量的吸收途径。ABC 转运体具有广泛的底物谱,是镉和镉复合物的主要细胞外流途径。在本综述中,我们总结了目前有关 ABC 转运体 ABCB1(P-糖蛋白,MDR1)、ABCB6、ABCC1(多药耐药性相关蛋白 1,MRP1)、ABCC7(囊性纤维化跨膜调节因子,CFTR)和 ABCG2(乳腺癌相关蛋白,BCRP)转运镉及其复合物(主要是与谷胱甘肽结合的镉)的知识。讨论了 ABC 转运体介导的镉和镉复合物外排的潜在解毒策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cadmium transport by mammalian ATP-binding cassette transporters

Cadmium transport by mammalian ATP-binding cassette transporters

Cellular responses to toxic metals depend on metal accessibility to intracellular targets, reaching interaction sites, and the intracellular metal concentration, which is mainly determined by uptake pathways, binding/sequestration and efflux pathways. ATP-binding cassette (ABC) transporters are ubiquitous in the human body—usually in epithelia—and are responsible for the transfer of indispensable physiological substrates (e.g. lipids and heme), protection against potentially toxic substances, maintenance of fluid composition, and excretion of metabolic waste products. Derailed regulation and gene variants of ABC transporters culminate in a wide array of pathophysiological disease states, such as oncogenic multidrug resistance or cystic fibrosis. Cadmium (Cd) has no known physiological role in mammalians and poses a health risk due to its release into the environment as a result of industrial activities, and eventually passes into the food chain. Epithelial cells, especially within the liver, lungs, gastrointestinal tract and kidneys, are particularly susceptible to the multifaceted effects of Cd because of the plethora of uptake pathways available. Pertinent to their broad substrate spectra, ABC transporters represent a major cellular efflux pathway for Cd and Cd complexes. In this review, we summarize current knowledge concerning transport of Cd and its complexes (mainly Cd bound to glutathione) by the ABC transporters ABCB1 (P-glycoprotein, MDR1), ABCB6, ABCC1 (multidrug resistance related protein 1, MRP1), ABCC7 (cystic fibrosis transmembrane regulator, CFTR), and ABCG2 (breast cancer related protein, BCRP). Potential detoxification strategies underlying ABC transporter-mediated efflux of Cd and Cd complexes are discussed.

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来源期刊
Biometals
Biometals 生物-生化与分子生物学
CiteScore
5.90
自引率
8.60%
发文量
111
审稿时长
3 months
期刊介绍: BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.
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