A Sluggish Response to Humanity's Biggest Mass Poisoning

Bhattacharjee, Yudhijit

doi:10.1126/science.315.5819.1659

Cited by 38 publications

(21 citation statements)

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“…In yeast, vacuolar acidification is involved in secondary transport of variety of ions and metabolites (40). It is known that arsenic is removed from the cells via sequestration of As(GS) 3 into vacuoles (28).…”

Section: Discussionmentioning

confidence: 99%

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Vujcic

Shroff²,

Singh³

2007

Cancer Research

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We have used yeast Saccharomyces cerevisiae as a tool to identify the importance of mitochondrial processes involved in arsenic-induced carcinogenicity in humans. We screened 466 single-gene knockout strains of yeast S. cerevisiae known to be involved in biogenesis of mitochondria for sodium arsenite (AsIII) and sodium arsenate (AsV) sensitivity. We identified 72 arsenite-sensitive and 81 arsenate-sensitive mutants. We categorized the identified mutants based on the various mitochondrial processes, including nucleic acid metabolism, oxidative phosphorylation, protein synthesis, and vacuolar acidification. We have identified 65 human orthologues to proteins involved in arsenite sensitivity and 3 human orthologues to arsenite resistance. Furthermore, 23 human orthologues to arsenate sensitivity and 20 human orthologues to arsenate-resistant proteins, including MSH3, COX10, GCSH, PPOX, and MTHFD1, were also identified. Using PathwayAssist software, we did cellular network analysis between identified mitochondrial proteins. Three types of interactions, (a) protein-protein interactions, (b) common transcriptional regulators, and (c) common target genes, were identified. We found that RTG (retrograde) genes involved in mitochondria-to-nucleus signaling regulate both arsenite sensitivity and resistance. Furthermore, our study revealed that ABF1, a multifunctional transcriptional factor, regulates genes involved in both arsenite and arsenate sensitivity and resistance. However, REB1 and RAP1 transcriptional regulators were common to only arsenate-and arsenite-sensitive genes, respectively. These studies indicate that multiple pathways involved in mitochondrial biogenesis protect yeast S. cerevisiae from arsenic-induced toxicity. Together, our studies suggest that evolutionary conserved mitochondrial networks identified in yeast S. cerevisiae must play an important role in arsenic-induced carcinogenesis in humans.

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Section: Discussionmentioning

confidence: 99%

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Vujcic

Shroff²,

Singh³

2007

Cancer Research

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“…These transporters are classified into four major subfamilies based on their homology and localization: plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26-like intrinsic membrane proteins (NIPs), and small and basic intrinsic proteins (SIPs) (19). Arsenite, with a pK a of 9.2, is present predominantly as uncharged molecules of arsenous acid [As(OH) 3 ] at pH Ͻ 8. Recently, a NIP transporter (Lsi1) for silicic acid, which is also uncharged at pH Ͻ 8, has been identified in rice (20).…”

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confidence: 99%

Transporters of arsenite in rice and their role in arsenic accumulation in rice grain

Feng

Yamaji

Mitani

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

1,209

861

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Arsenic poisoning affects millions of people worldwide. Human arsenic intake from rice consumption can be substantial because rice is particularly efficient in assimilating arsenic from paddy soils, although the mechanism has not been elucidated. Here we report that two different types of transporters mediate transport of arsenite, the predominant form of arsenic in paddy soil, from the external medium to the xylem. Transporters belonging to the NIP subfamily of aquaporins in rice are permeable to arsenite but not to arsenate. Mutation in OsNIP2;1 (Lsi1, a silicon influx transporter) significantly decreases arsenite uptake. Furthermore, in the rice mutants defective in the silicon efflux transporter Lsi2, arsenite transport to the xylem and accumulation in shoots and grain decreased greatly. Mutation in Lsi2 had a much greater impact on arsenic accumulation in shoots and grain in field-grown rice than Lsi1. Arsenite transport in rice roots therefore shares the same highly efficient pathway as silicon, which explains why rice is efficient in arsenic accumulation. Our results provide insight into the uptake mechanism of arsenite in rice and strategies for reducing arsenic accumulation in grain for enhanced food safety.efflux ͉ influx ͉ arsenic contamination ͉ silicon ͉ aquaporin A rsenic (As) is a human carcinogen, and there may be no threshold below which it does not cause cancer (1). More than 40 million people worldwide are at risk from drinking As-contaminated groundwater (2), and chronic inorganic As poisoning has reached a massive scale in Bangladesh and West Bengal, India (3). In these countries, As-contaminated groundwater is also widely used for irrigating crops during dry season rice production, adding Ͼ1,000 metric tons of As to soil per year in Bangladesh alone and resulting in As accumulation in soils and elevated As uptake by crops (4-6). Elevated As accumulation in rice has the potential to become a new disaster for the population in Southeast Asia (7). As concentrations in rice grain are often high enough to cause concern even in uncontaminated soils containing background levels of As, because paddy rice appears to be particularly efficient in As assimilation compared with other cereal crops (8). Worldwide market surveys show that rice grain contains considerably higher levels of inorganic As than other foods (9, 10). Human intake of As from consumption of rice can be substantial, especially for people who consume a lot of rice (11). It is therefore crucial that the mechanism of As accumulation in rice is understood to counteract this widespread contamination of the food chain.Plants take up arsenate, the predominant form of As in aerobic soils, through phosphate transporters (12, 13). However, in paddy soils, which are flooded during much of the rice growing season, arsenite becomes the predominant chemical species of As (14). It has been shown that arsenite is taken up via aquaglyceroporins in microbes (13,(15)(16)(17). Evidence from physiological studies suggests that arsenite may also be transp...

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“…Consequently, Ahmed and co-workers have insisted on regular monitoring of water quality regardless of the mitigation technique, broader public awareness campaigns, and the wise use of the water sources that are low in arsenic (Ahmed et al 2006). However, the issue currently remains unresolved (Ball 2005;Bhattacharjee 2007).…”

Section: Introductionmentioning

confidence: 96%

Pollution magnet: nano-magnetite for arsenic removal from drinking water

Yavuz

Mayo

Suchecki

et al. 2010

Environ Geochem Health

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Arsenic contamination in groundwater is a severe global problem, most notably in Southeast Asia where millions suffer from acute and chronic arsenic poisoning. Removing arsenic from groundwater in impoverished rural or urban areas without electricity and with no manufacturing infrastructure remains a significant challenge. Magnetite nanocrystals have proven to be useful in arsenic remediation and could feasibly be synthesized by a thermal decomposition method that employs refluxing of FeOOH and oleic acid in 1-octadecene in a laboratory setup. To reduce the initial cost of production, $US 2600/kg, and make this nanomaterial widely available, we suggest that inexpensive and accessible "everyday" chemicals be used. Here we show that it is possible to create functional and high-quality nanocrystals using methods appropriate for manufacturing in diverse and minimal infrastructure, even those without electricity. We suggest that the transfer of this knowledge is best achieved using an open source concept.

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A Sluggish Response to Humanity's Biggest Mass Poisoning

Cited by 38 publications

References 0 publications

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Transporters of arsenite in rice and their role in arsenic accumulation in rice grain

Pollution magnet: nano-magnetite for arsenic removal from drinking water

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