Roles of vertebrate aquaglyceroporins in arsenic transport and detoxification.

Abstract

Aquaporins are important channel proteins that are responsible for the balance of cellular osmolarity and nutrient transport in vertebrates. Recently, new functions of these ancient channels have been found in the conduction of metalloid arsenic (As). Chronic As exposure through contaminated water and food sources is associated with multiple human diseases and endangers millions of people's health worldwide. Therefore, identification of the As transport pathways is necessary to elucidate the mechanisms of As carcinogenesis. Arsenic detoxification systems have been studied in multiple vertebrates such as mammalian mouse, rat, humans and nonmammalian vertebrates. Multiple transporters and enzymes have been shown to be involved in As translocation and cellular transformation. In these vertebrates, members ofaquaglyceroporins, which include AQP7 in kidney and AQP9 in liver, catalyze uptake of inorganic trivalent arsenite [As(III)]. AQP9, the major liver aquaglyceroporin, conducts both inorganic As(III) and organic monomethylarsonous acid [MMA(III)], an intermediate that is generated during the cellular methylation. As a channel that facilitates a downhill movement of substances dependent on the concentration gradient, AQP9 may play an important role in the simultaneous influx of inorganic As(III) from blood to liver and efflux of As metabolite MMA(III) from liver to blood. In this chapter, we will discuss the function ofaquaglyceroporins ofvertebrates in uptake and detoxification of the metalloid As.