Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Abstract

Much is known about the transport of arsenite and antimonite into microbes, but the identities of mammalian transport proteins are unknown. The Saccharomyces cerevisiae FPS1 gene encodes a membrane protein homologous to the bacterial aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock. Fps1p has been shown to facilitate uptake of the metalloids arsenite and antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and sensitivity to metalloid salts. In this study, the ability of mammalian aquaglyceroporins AQP7 and AQP9 to substitute for the yeast Fps1p was examined. The fps1⌬ strain of S. cerevisiae exhibits increased tolerance to arsenite and antimonite compared to a wild-type strain. Introduction of a plasmid containing AQP9 reverses the metalloid tolerance of the deletion strain. AQP7 was not expressed in yeast. The fps1⌬ cells exhibit reduced transport of 73 As(III) or 125 Sb(III), but uptake is enhanced by expression of AQP9. Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited increased transport of 73 As(III). These results suggest that AQP9 and AQP7 may be a major routes of arsenite uptake into mammalian cells, an observation potentially of large importance for understanding the action of arsenite as a human toxin and carcinogen, as well as its efficacy as a chemotherapeutic agent for acute promyelocytic leukemia.Fps1p ͉ GlpF ͉ acute promyelocytic leukemia

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

“…However, in the arsenic uptake and cytotoxicity assay, the OATP-C increased uptake and cytotoxicity of arsenic was not as much as that of E 2 17bG. It is possible that there are other pathways for arsenic uptake by cells other than OATP-C [28,29,41]. For example, Hung and Lee [41] indicated that As III can be freely taken up by cells through simple diffusion, and As V shares a common transport system with phosphate in cells.…”

“…For example, Hung and Lee [41] indicated that As III can be freely taken up by cells through simple diffusion, and As V shares a common transport system with phosphate in cells. On the other hand, recent reports have shown that AQP9 and AQP7 can cause uptake of arsenite into mammalian cells [28].…”

“…In S. cerevisiae, the GlpF homolog Fps1p is involved in arsenic uptake. In mammalian cells, the aquaglyceroporins AQP7 and AQP9 have been shown to uptake arsenite [28,29].…”

The tobacco geneNtcyc07confers arsenite tolerance inSaccharomyces cerevisiaeby reducing the steady state levels of intracellular arsenic

“…For example, a chromate-tolerant mutant of S. cerevisiae accumulates lower amounts of Cr than the WT [33,34]. In addition, we have shown that either decreasing As(III) uptake by deletion of FPS1 [35] or increasing efflux by induction of ACR3 [36] will confer As(III) tolerance in S. cerevisae. To examine whether the increased As(III) tolerance of Y800-Ntcyc07 is related to alteration of the steady state levels of arsenic, the amount of arsenic was measured in cells cultured for 24 h in ura(À) CM medium with 50 lM sodium arsenite (Fig.…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…Although not previously related to PD, several lines of evidence argue for a link between these. AQP9 is an aquaglyceroporin with particularly broad substance permeability, transporting water, glycerol, monocarboxylates and arsenite, among others (10)(11)(12)(13)(14). This water channel has recently been found to be selectively expressed in dopaminergic plasma membranes as well as mitochondrial inner membranes in the SN (15)(16)(17), indicating that it may serve as a toxin influx route into these cells, thereby accounting for an increased susceptibility to cell death.…”