Roles of Vertebrate Aquaglyceroporins in Arsenic Transport and Detoxification

Liu, Zijuan

doi:10.1007/978-1-4419-6315-4_6

Cited by 22 publications

(11 citation statements)

References 62 publications

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“…As noted earlier, aquaglyceroporins can act as conduits for substrates other than water. For instance, some aquaporins have been shown to play a role in controlling the exchange of metalloids (like arsenic and antimony) between an organism and its environment (Sanders et al , 1997; Liu, 2010). Some such metalloids have been used therapeutically and, until relatively recently, an important treatment option for schistosome infection involved the use of trivalent antimonials such as potassium antimony tartrate (Rodriguez-Molina et al , 1950; Bueding & Mansour, 1957).…”

Section: Water Transportmentioning

confidence: 99%

Metabolite movement across the schistosome surface

et al. 2012

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Intravascular schistosome parasites are covered by an unusual double lipid bilayer. Nutrients, such as glucose and amino acids, as well as other metabolites, are known to be transported across this surface via specific transporter proteins. For instance, the glucose transporter protein SGTP4 is found in the host-interactive tegumental membranes. A second glucose transporter, SGTP1, localizes to the tegumental basal membrane (and internal tissues). Following expression in Xenopus oocytes, SGTP1 and SGTP4 both function as facilitated-diffusion sugar transporters. Suppressing the expression of SGTP1 and SGTP4 in juvenile schistosomes using RNA interference (RNAi) impairs the parasite's ability to import glucose and severely decreases worm viability. Amino acids can also be imported into schistosomes across their surface and an amino acid transporter (SPRM1lc) has been localized in the parasite surface membranes (as well as internally). In Xenopus oocytes, SPRM1lc can import the basic amino acids arginine, lysine and histidine as well as leucine, phenylalanine, methionine and glutamine. To function, this protein requires the assistance of a heavy-chain partner (SPRM1hc) which acts as a chaperone. Water is transported across the tegument of schistosomes via the aquaporin protein SmAQP. Suppressing SmAQP gene expression makes the parasites less able to osmoregulate and decreases their viability. In addition, SmAQP-suppressed adult parasites have been shown to be impaired in their ability to excrete lactate. Analysis of tegumental transporter proteins, as described in this report, is designed to generate a comprehensive understanding of the role of such proteins in promoting parasite survival by controlling the movement of metabolites into and out of the worms.

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Section: Water Transportmentioning

confidence: 99%

Metabolite movement across the schistosome surface

et al. 2012

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“…Aquaporins are passive transporters, but because of the electrostatic field across cell membranes, they are more likely to efflux negatively charged compounds of arsenic. The mammalian aquaporin AQP9 has been shown to transport MMA, as well as MMA and DMA (24).…”

Section: Resultsmentioning

confidence: 99%

A Parasitic Arsenic Cycle That Shuttles Energy from Phytoplankton to Heterotrophic Bacterioplankton

Giovannoni

Halsey

Saw

et al. 2019

mBio

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In many regions of the world oceans, phytoplankton face the problem of discriminating between phosphate, an essential nutrient, and arsenate, a toxic analogue. Many phytoplankton, including the most abundant phytoplankton group known,Prochlorococcus, detoxify arsenate (AsV) by reduction to arsenite (AsIII), followed by methylation and excretion of the methylated arsenic products. We synthesized [14C]dimethyl arsenate (DMA) and used it to show that culturedPelagibacterstrain HTCC7211 (SAR11) cells oxidize the methyl group carbons of DMA, producing14CO2and ATP. We measured [14C]DMA oxidation rates in the P-depleted surface waters of the Sargasso Sea, a subtropical ocean gyre. [14C]DMA was oxidized to14CO2by Sargasso Sea plankton communities at a rate that would cause turnover of the estimated DMA standing stock every 8.1 days. SAR11 strain HTCC7211, which was isolated from the Sargasso Sea, has a pair of arsenate resistance genes and was resistant to arsenate, showing no growth inhibition at As/P ratios of >65:1. Across the global oceans, there was a strong inverse relationship between the frequency of the arsenate reductase (LMWPc_ArsC) inPelagibactergenomes and phosphate concentrations. We propose that the demethylation of methylated arsenic compounds byPelagibacterand possibly other bacterioplankton, coupled with arsenate resistance, results in the transfer of energy from phytoplankton to bacteria. We dub this a parasitic cycle because the release of arsenate byPelagibacterin principle creates a positive-feedback loop that forces phytoplankton to continually regenerate arsenate detoxification products, producing a flow of energy to P-limited ocean regions.IMPORTANCEIn vast, warm regions of the oceans, phytoplankton face the problem of arsenic poisoning. Arsenate is toxic because it is chemically similar to phosphate, a scarce nutrient that phytoplankton cells need for growth. Many phytoplankton, including the commonest phytoplankton type in warm oceans,Prochlorococcus, detoxify arsenate by adding methyl groups. Here we show that the most abundant non-photosynthetic plankton in the oceans, SAR11 bacteria, remove the methyl groups, releasing poisonous forms of arsenic back into the water. We postulate that the methylation and demethylation of arsenic compounds creates a cycle in which the phytoplankton can never get ahead and must continually transfer energy to the SAR11 bacteria. We dub this a parasitic process and suggest that it might help explain why SAR11 bacteria are so successful, surpassing all other plankton in their numbers. Field experiments were done in the Sargasso Sea, a subtropical ocean gyre that is sometimes called an ocean desert because, throughout much of the year, there is not enough phosphorous in the water to support large blooms of phytoplankton. Ocean deserts are expanding as the oceans absorb heat and grow warmer.

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“…Notably, drug conjugation with GSH can occur either spontaneously or by catalytic action via the GST enzyme subclass P1 (26,27). In models using arsenic (As), a metal closely related to Sb, an increase in the expression of GST-P in mouse cell lines has been reported, resulting in an increase in cellular tolerance to arsenic through the formation of drug conjugates with GSH and ABC drug transporter family efflux of As (28,29). The increased protein expression of GSTP1 observed in the present study suggests that this enzyme may play a role similar to that described for As detoxification, by forming Sb conjugates with GSH to efflux Sb from human macrophages.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Host Antioxidant Defense Genes Enhances the Effect of Glucantime on Intracellular Leishmania braziliensis in Human Macrophages

Téllez

Romero

Soares

et al. 2017

Antimicrob Agents Chemother

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Leishmaniasis is a neglected tropical disease that affects millions of people worldwide and represents a major public health problem. Information on protein expression patterns and functional roles within the context of Leishmaniainfected human monocyte-derived macrophages (MDMs) under drug treatment conditions is essential for understanding the role of these cells in leishmaniasis treatment. We analyzed functional changes in the expression of human MDM genes and proteins during in vitro infection by Leishmania braziliensis and treatment with Glucantime (Sb V ), using quantitative PCR (qPCR) arrays, Western blotting, confocal microscopy, and small interfering RNA (siRNA) human gene inhibition assays. Comparison of the results from gene transcription and protein expression analyses revealed that glutathione S-transferase 1 (GSTP1), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GSR), glutathione synthetase (GSS), thioredoxin (TRX), and ATP-binding cassette, subfamily B, member 5 (ABCB5), were strongly upregulated at both the mRNA and protein levels in human MDMs that were infected and treated, compared to the control group. Subcellular localization studies showed a primarily phagolysosomal location for the ABCB5 transporter, indicating that this protein may be involved in the transport of Sb V . By inducing a decrease in L. braziliensis intracellular survival in THP-1 macrophages, siRNA silencing of GSTP1, GSS, and ABCB5 resulted in an increased leishmanicidal effect of Sb V exposure in vitro. Our results suggest that human MDMs infected with L. braziliensis and treated with Sb V express increased levels of genes participating in antioxidant defense, whereas our functional analyses provide evidence for the involvement of human MDMs in drug detoxification. Therefore, we conclude that GSS, GSTP1, and ABCB5 proteins represent potential targets for enhancing the leishmanicidal activity of Glucantime.KEYWORDS human leishmaniasis, host-pathogen interaction, Leishmania braziliensis, GSTP1, GSS, ABCB5, Glucantime L eishmania spp., which are intracellular protozoan parasites, are the causative agents of leishmaniasis, a neglected infectious disease that is found worldwide. Depending on the species of infecting parasite and the host immune status, leishmaniasis can manifest in a variety of clinical conditions with cutaneous, mucocutaneous, or visceral involvement (1, 2). Leishmania (Viannia) braziliensis, which causes cutaneous and mucocutaneous leishmaniasis, is the most prevalent species infecting humans in Central America and South America (3). Currently, the control of leishmaniasis depends

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Roles of Vertebrate Aquaglyceroporins in Arsenic Transport and Detoxification

Cited by 22 publications

References 62 publications

Metabolite movement across the schistosome surface

Metabolite movement across the schistosome surface

A Parasitic Arsenic Cycle That Shuttles Energy from Phytoplankton to Heterotrophic Bacterioplankton

Knockdown of Host Antioxidant Defense Genes Enhances the Effect of Glucantime on Intracellular Leishmania braziliensis in Human Macrophages

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