砷化合物的摄入调控机制

The regulation mechanism of the arsenical uptake

流行病学结果显示慢性砷暴露可导致人群罹患皮肤癌、膀胱癌、肺癌等恶性疾病,但其致毒/癌机制尚不明确.目前关于砷暴露致毒/癌机理的讨论主要集中在砷的胞内作用途径,而较少关注砷摄入调控过程对其暴露致毒/癌的贡献.在生理条件下,部分砷化合物由于结构与磷酸根、葡萄糖、甘油等天然底物相近,可借由相应的载体被细胞摄入,摄入途径和效率存在显著的砷形态依赖性.此外,砷化合物的生物毒性效应与其赋存形态直接相关.可见,砷的摄入调控对于砷的暴露致毒/癌具有重要作用.本文主要综述了在哺乳动物体系中不同砷形态的摄入载体、载体调控及对应的砷摄入分布、效率和暴露毒性,在此基础上,强调了以往在砷致毒/癌机制研究中被忽视的砷摄入调控途径.然而,砷摄入调控过程中的诸多重要环节如砷胁迫下的摄入启动和调控机制等都是空白,需进一步系统深入地研究,为深入理解砷的致毒机制提供了新的视角和研究思路.

The epidemiological results demonstrate that chronic exposure to inorganic arsenic is closely associated with the malignant diseases of skin,bladder and lung cancer,however,the molecular toxicity mechanism has not been clarified.The related studies mainly focus on the interaction of arsenicals inside cells,while the transmembrane transport of arsenicals has been overlooked.Some arsenicals can enter into cells by the transporters specific for the natural substrates of phosphate,glucose and glycerol,because of their similar structure under the physiological conditions.Furthermore,the transport pathway and efficiency are significantly dependent on the arsenic species.Meanwhile,the toxic effects upon arsenic exposure vary a lot with different species.Thus,it is speculated that the regulation of arsenical uptake plays an important role in the toxicological/carcinogenic effects.Herein,we reviewed the transporters and their regulation signaling in mammalian system for transmembrane transport of different arsenic species.And the uptake efficiency,distribution,and resultant toxicity of arsenicals in terms of species has also been summarized.In this term,the uptake regulation of arsenicals has been emphasized in the research of the toxicological/carcinogenic mechanism upon arsenic exposure.Nevertheless,several key steps in the course of arsenic uptake,like the patterns for uptake initiation and regulation are scarcely studied,which deserve further investigation in detail.This review provides new insights into the toxicity mechanism for arsenic exposure.