Bhattacharjee Hiranmoy, Rosen Barry P, Mukhopadhyay Rita
Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI, 48201, USA.
Handb Exp Pharmacol. 2009(190):309-25. doi: 10.1007/978-3-540-79885-9_16.
Aquaglyceroporin (AQP) channels facilitate the diffusion of a wide range of neutral solutes, including water, glycerol, and other small uncharged solutes. More recently, AQPs have been shown to allow the passage of trivalent arsenic and antimony compounds. Arsenic and antimony are metalloid elements. At physiological pH, the trivalent metalloids behave as molecular mimics of glycerol, and are conducted through AQP channels. Arsenicals and antimonials are extremely toxic to cells. Despite their toxicity, both metalloids are used as chemotherapeutic agents for the treatment of cancer and protozoan parasitic diseases. The metalloid homeostasis property of AQPs can be a mixed blessing. In some cases, AQPs form part of the detoxification pathway, and extrude metalloids from cells. In other instances, AQPs allow the transport of metalloids into cells, thereby conferring sensitivity. Understanding the factors that modulate AQP expression will aid in a better understanding of metalloid toxicity and also provide newer approaches to metalloid based chemotherapy.
水甘油通道蛋白(AQP)促进多种中性溶质的扩散,包括水、甘油和其他不带电荷的小分子溶质。最近研究表明,水甘油通道蛋白能让三价砷和锑化合物通过。砷和锑属于类金属元素。在生理pH值下,三价类金属表现为甘油的分子模拟物,并通过水甘油通道蛋白通道传导。砷化合物和锑化合物对细胞具有极强的毒性。尽管它们有毒,但这两种类金属都被用作治疗癌症和原生动物寄生虫病的化疗药物。水甘油通道蛋白的类金属稳态特性可能是一把双刃剑。在某些情况下,水甘油通道蛋白构成解毒途径的一部分,并将类金属排出细胞。在其他情况下,水甘油通道蛋白允许类金属进入细胞,从而使细胞产生敏感性。了解调节水甘油通道蛋白表达的因素将有助于更好地理解类金属毒性,并为基于类金属的化疗提供新方法。