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Caenorhabditis elegans gcs-1 Confers Resistance to Arsenic-Induced Oxidative Stress

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Abstract

Gamma-glutamylcysteine synthetase (γ-GCS) catalyzes the first, rate-limiting step in the biosynthesis of glutathione (GSH). To evaluate the protective role of cellular GSH against arsenic-induced oxidative stress in Caenorhabditis elegans (C. elegans), we examined the effect of the C. elegans ortholog of GCS(h), gcs-1, in response to inorganic arsenic exposure. We have evaluated the responses of wild-type and gcs-1 mutant nematodes to both inorganic arsenite (As(III)) and arsenate (As(V)) ions and found that gcs-1 mutant nematodes are more sensitive to arsenic toxicity than that of wild-type animals. The amount of metal ion required to kill half of the population of worms falls in the order of wild-type/As(V)>gcs-1/As(V)> wild-type/As(III)>gcs-1/As(III). gcs-1 mutant nematodes also showed an earlier response to the exposure of As(III) and As(V) than that of wild-type animals. Pretreatment with GSH significantly raised the survival rate of gcs-1 mutant worms compared to As(III)- or As(V)-treated worms alone. These results indicate that GCS-1 is essential for the synthesis of intracellular GSH in C. elegans and consequently that the intracellular GSH status plays a critical role in protection of C. elegans from arsenic-induced oxidative stress.

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References

  • CO Abernathy YP Liu D Longfellow HV Aposhian B Beck B Fowler R Goyer R Menzer T Rossman C Thompson M Waalkes (1999) ArticleTitleArsenic: health effects, mechanisms of actions, and research issues Environ Health Perspect 107 593–597 Occurrence Handle10379007 Occurrence Handle1:CAS:528:DyaK1MXltVSktbg%3D

    PubMed  CAS  Google Scholar 

  • JH An TK Blackwell (2003) ArticleTitleSKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response Genes Dev 17 1882–1893 Occurrence Handle10.1101/gad.1107803 Occurrence Handle12869585 Occurrence Handle1:CAS:528:DC%2BD3sXmt1Sjt7w%3D

    Article  PubMed  CAS  Google Scholar 

  • InstitutionalAuthorNameAgency for Toxic Substances and Disease Registry (2000) Toxicological profile for arsenic (PB/2000/108021) U.S. Department of Health and Human Services, Public Health Service Washington, DC

    Google Scholar 

  • JC Barrett PW Lamb TC Wang TC Lee (1989) ArticleTitleMechanisms of arsenic-induced cell transformation Biol Trace Elem Res 21 421–429 Occurrence Handle2484623 Occurrence Handle1:STN:280:DyaK3M%2FgtFegsA%3D%3D

    PubMed  CAS  Google Scholar 

  • S Brenner (1974) ArticleTitleThe genetics of Caenorhabditis elegans Genetics 77 71–94 Occurrence Handle4366476 Occurrence Handle1:STN:280:DyaE2c3ntFWlsw%3D%3D

    PubMed  CAS  Google Scholar 

  • A Broeks B Gerrard R Allikmets M Dean RH Plasterk (1996) ArticleTitleHomologues of the human multidrug resistance genes MRP and MDR contribute to heavy metal resistance in the soil nematode Caenorhabditis elegans EMBO J 15 6132–6143 Occurrence Handle8947035 Occurrence Handle1:CAS:528:DyaK28XnsFKktbg%3D

    PubMed  CAS  Google Scholar 

  • L Canesi C Ciacci G Piccoli V Stocchi A Viarengo G Gallo (1998) ArticleTitle In vitro and in vivo effects of heavy metals on mussel digestive gland hexokinase activity: the role of glutathione Comp Biochem Physiol 120 261–268 Occurrence Handle1:STN:280:DyaK1M%2FksVaktA%3D%3D

    CAS  Google Scholar 

  • M Cavigelli WW Li A Lin B Su K Yoshioka M Karin (1996) ArticleTitleThe tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase EMBO J 15 6269–6279 Occurrence Handle8947050 Occurrence Handle1:CAS:528:DyaK28XnsFOgtb8%3D

    PubMed  CAS  Google Scholar 

  • WC Chou AL Hawkins JF Barrett CA Griffin CV Dang (2001) ArticleTitleArsenic inhibition of telomerase transcription leads to genetic instability J Clin Invest 108 1541–1547 Occurrence Handle10.1172/JCI200114064 Occurrence Handle11714746 Occurrence Handle1:CAS:528:DC%2BD3MXosVyru78%3D

    Article  PubMed  CAS  Google Scholar 

  • J Dai RS Weinberg S Waxman Y Jing (1999) ArticleTitleMalignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system Blood 93 268–277 Occurrence Handle9864170 Occurrence Handle1:CAS:528:DyaK1MXhvFSrtQ%3D%3D

    PubMed  CAS  Google Scholar 

  • LM Del Razo M Styblo WR Cullen DJ Thomas (2001) ArticleTitleDetermination of trivalent methylated arsenicals in biological matrices Toxicol Appl Pharmacol 174 282–293 Occurrence Handle10.1006/taap.2001.9226 Occurrence Handle11485389 Occurrence Handle1:CAS:528:DC%2BD3MXls1egtbg%3D

    Article  PubMed  CAS  Google Scholar 

  • M Delnomdedieu MM Basti JO Otvos DJ Thomas (1993) ArticleTitleTransfer of arsenite from glutathione to dithiol: a model of interaction Chem Res Toxicol 6 598–602 Occurrence Handle10.1021/tx00035a002 Occurrence Handle8292735 Occurrence Handle1:CAS:528:DyaK3sXmsVejurs%3D

    Article  PubMed  CAS  Google Scholar 

  • M Delnomdedieu MM Basti M Styblo JD Otvos DJ Thomas (1994) ArticleTitleComplexation of arsenic species in rabbit erythrocytes Chem Res Toxicol 7 621–627 Occurrence Handle10.1021/tx00041a006 Occurrence Handle7841340 Occurrence Handle1:CAS:528:DyaK2cXlsFSks7s%3D

    Article  PubMed  CAS  Google Scholar 

  • E Dudley CD Klaassen (1984) ArticleTitleChanges in hepatic glutathione concentration modify cadmium-induced hepatotoxicity Toxicol Appl Pharmacol 72 530–538 Occurrence Handle10.1016/0041-008X(84)90130-3 Occurrence Handle6710502 Occurrence Handle1:CAS:528:DyaL2cXhsFaitr4%3D

    Article  PubMed  CAS  Google Scholar 

  • L Eaton NH Stacey KL Wong CD Klaassen (1980) ArticleTitleDose–response effects of various metal ions on rat liver, metallothionein, glutathione, heme oxygenase and cytochrome P-450 Toxicol Appl Pharmacol 55 393–402 Occurrence Handle6893504 Occurrence Handle1:CAS:528:DyaL3cXlvVSmsbY%3D

    PubMed  CAS  Google Scholar 

  • M Kawasaki N Hisamoto Y Iino M Yamamoto J Ninomiya-Tsuji K Matsumoto (1999) ArticleTitleA Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons EMBO J 18 3604–3615 Occurrence Handle10.1093/emboj/18.13.3604 Occurrence Handle10393177 Occurrence Handle1:CAS:528:DyaK1MXksFKltr8%3D

    Article  PubMed  CAS  Google Scholar 

  • JH Freedman LW Slice D Dixon A Fire CS Rubin (1993) ArticleTitleThe novel metallothionein genes of Caenorhabditis elegans. Structural organization and inducible, cell-specific expression J Biol Chem 268 2554–2564 Occurrence Handle8428932 Occurrence Handle1:CAS:528:DyaK3sXitVKlsLg%3D

    PubMed  CAS  Google Scholar 

  • AM Giglio T Hunter JV Bannister WH Bannister G Hunter (1994) ArticleTitleThe copper/zinc superoxide dismutase gene of Caenorhabditis elegans Biochem Mol Biol Int 33 41–44 Occurrence Handle8081212 Occurrence Handle1:CAS:528:DyaK2cXlt1Kmsbw%3D

    PubMed  CAS  Google Scholar 

  • PL Goering HV Aposhian MJ Mass M Cebrian BD Beck MP Waalkes (1999) ArticleTitleThe enigma of arsenic carcinogenesis: role of metabolism Toxicol Sci 49 5–14 Occurrence Handle10.1093/toxsci/49.1.5 Occurrence Handle10367337 Occurrence Handle1:CAS:528:DyaK1MXjvVaktb8%3D

    Article  PubMed  CAS  Google Scholar 

  • HK Hamadeh M Vargas E Lee DB Menzel (1999) ArticleTitleArsenic disrupts cellular levels of p53 and mdm2: a potential mechanism of carcinogenesis Biochem Biophys Res Commun 263 446–449 Occurrence Handle10.1006/bbrc.1999.1395 Occurrence Handle10491313 Occurrence Handle1:CAS:528:DyaK1MXlvFanu7w%3D

    Article  PubMed  CAS  Google Scholar 

  • JD Hayes LI McLellan (1999) ArticleTitleGlutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress Free Radic Res 31 273–300 Occurrence Handle10517533 Occurrence Handle1:CAS:528:DyaK1MXmslGjsL8%3D

    PubMed  CAS  Google Scholar 

  • JD Hayes M McMahon (2001) ArticleTitleMolecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention Cancer Lett 174 103–113 Occurrence Handle10.1016/S0304-3835(01)00695-4 Occurrence Handle11689285 Occurrence Handle1:CAS:528:DC%2BD3MXnvFCktL8%3D

    Article  PubMed  CAS  Google Scholar 

  • MF Heschl DL Baillie (1990) ArticleTitleThe HSP70 multigene family of Caenorhabditis elegans Comp Biochem Physiol 96 633–637 Occurrence Handle1:STN:280:DyaK3M%2FjtVCltQ%3D%3D

    CAS  Google Scholar 

  • M Hirata A Tanaka A Hisanaga N Ishinishi (1990) ArticleTitleEffects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters Toxicol Appl Pharmacol 106 469–481 Occurrence Handle10.1016/0041-008X(90)90342-R Occurrence Handle2260095 Occurrence Handle1:CAS:528:DyaK3MXns1KjtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • IA Hope (1999) C. elegans: A Practical Approach Oxford Oxford University Press, UK: 62–63

    Google Scholar 

  • H Huang CF Huang DR Wu CM Jinn KY Jan (1993) ArticleTitleGlutathione as a cellular defense against arsenite toxicity in cultured Chinese hamster ovary cells Toxicology 79 195–204 Occurrence Handle10.1016/0300-483X(93)90211-A Occurrence Handle8316949 Occurrence Handle1:CAS:528:DyaK3sXltFWjtrs%3D

    Article  PubMed  CAS  Google Scholar 

  • KT Kitchin (2001) ArticleTitleRecent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites Toxicol Appl Pharmacol 172 249–261 Occurrence Handle10.1006/taap.2001.9157 Occurrence Handle11312654 Occurrence Handle1:CAS:528:DC%2BD3MXivVehtr0%3D

    Article  PubMed  CAS  Google Scholar 

  • M Land A Islas-Trejo CS Rubin (1994) ArticleTitleStructure and expression of a novel, neuronal protein kinase C (PKC1B) from Caenorhabditis elegans. PKC1B is expressed selectively in neurons that receive, transmit, and process environmental signals J Biol Chem 269 14820–14827 Occurrence Handle8182089 Occurrence Handle1:CAS:528:DyaK2cXktVagtro%3D

    PubMed  CAS  Google Scholar 

  • SA Lerman TW Clarkson RJ Gerson (1983) ArticleTitleArsenic uptake and metabolism by liver cells is dependent on arsenic oxidation state Chem Biol Interact 45 401–406 Occurrence Handle6883581 Occurrence Handle1:CAS:528:DyaL3sXlvV2hsbY%3D Occurrence Handle10.1016/0009-2797(83)90087-X

    Article  PubMed  CAS  Google Scholar 

  • M Li JF Cai JF Chiu (2002) ArticleTitleArsenic induces oxidative stress and activates stress gene expressions in cultured lung epithelial cells J Cell Biochem 87 29–38 Occurrence Handle12210719 Occurrence Handle1:CAS:528:DC%2BD38XmvFOnsLk%3D

    PubMed  CAS  Google Scholar 

  • VH Liao JH Freedman (2002) ArticleTitleDifferential display analysis of gene expression in invertebrates Cell Mol Life Sci 59 1256–1263 Occurrence Handle12363029 Occurrence Handle1:CAS:528:DC%2BD38XntFGlsrw%3D Occurrence Handle10.1007/s00018-002-8504-9

    Article  PubMed  CAS  Google Scholar 

  • VH Liao J Dong JH Freedman (2002) ArticleTitleMolecular characterization of a novel, cadmium-inducible gene from the nematode Caenorhabditis elegans. A new gene that contributes to the resistance to cadmium toxicity J Biol Chem 277 42049–42059 Occurrence Handle12189149 Occurrence Handle1:CAS:528:DC%2BD38XotF2gt70%3D

    PubMed  CAS  Google Scholar 

  • VH Liao JH Freedman (2001) ArticleTitleCharacterization of a cadmium-inducible isoform of pyruvate carboxylase from Caenorhabditis elegans DNA Seq 12 137–145 Occurrence Handle11761713 Occurrence Handle1:CAS:528:DC%2BD38Xks1ykurc%3D

    PubMed  CAS  Google Scholar 

  • VH Liao JH Freedman (1998) ArticleTitleCadmium-regulated genes from the nematode Caenorhabditis elegans. Identification and cloning of new cadmium-responsive genes by differential display J Biol Chem 273 31962–31970 Occurrence Handle9822667 Occurrence Handle1:CAS:528:DyaK1cXnvVelt74%3D

    PubMed  CAS  Google Scholar 

  • A Meister ME Anderson (1983) ArticleTitleGlutathione Annu Rev Biochem 52 711–760 Occurrence Handle10.1146/annurev.bi.52.070183.003431 Occurrence Handle6137189 Occurrence Handle1:CAS:528:DyaL3sXkvVektbs%3D

    Article  PubMed  CAS  Google Scholar 

  • K Nakamuro Y Sayato (1981) ArticleTitleComparative studies of chromosomal aberration induced by trivalent and pentavalent arsenic Mutat Res 88 73–80 Occurrence Handle7207493 Occurrence Handle1:CAS:528:DyaL3MXnvVWgtg%3D%3D

    PubMed  CAS  Google Scholar 

  • InstitutionalAuthorNameNRC (1999) Arsenic in Drinking Water Washington, DC National Research Council

    Google Scholar 

  • T Ochi (1997) ArticleTitleArsenic compound-induced increases in glutathione levels in cultured Chinese hamster V79 cells and mechanisms associated with changes in gamma-glutamylcysteine synthetase activity, cystine uptake and utilization of cysteine Arch Toxicol 71 730–740 Occurrence Handle10.1007/s002040050454 Occurrence Handle9388005 Occurrence Handle1:CAS:528:DyaK2sXms1eqtLY%3D

    Article  PubMed  CAS  Google Scholar 

  • T Ochi T Kaise Y Oya-Ohta (1994) ArticleTitleGlutathione plays different roles in the induction of the cytotoxic effects of inorganic and organic arsenic compounds in cultured BALB/c 3T3 cells Experientia 50 115–120 Occurrence Handle10.1007/BF01984946 Occurrence Handle8125168 Occurrence Handle1:CAS:528:DyaK2cXitFSgtrc%3D

    Article  PubMed  CAS  Google Scholar 

  • KL Oden TB Gladysheva BP Rosen (1994) ArticleTitleArsenate reduction mediated by the plasmid-encoded ArsC protein is coupled to glutathione Mol Microbiol 12 301–306 Occurrence Handle8057854 Occurrence Handle1:CAS:528:DyaK2cXktVCkurw%3D

    PubMed  CAS  Google Scholar 

  • Y Oya-Ohta T Kaise T Ochi (1996) ArticleTitleInduction of chromosomal aberrations in cultured human fibroblasts by inorganic and organic arsenic compounds and the different roles of glutathione in such induction Mutat Res 357 123–129 Occurrence Handle8876688 Occurrence Handle1:CAS:528:DyaK28XlvVeitrY%3D

    PubMed  CAS  Google Scholar 

  • A Pompella A Visvikis A Paolicchi V Tata ParticleDe AF Casini (2003) ArticleTitleThe changing faces of glutathione, a cellular protagonist Biochem Pharmacol 66 1499–1503 Occurrence Handle10.1016/S0006-2952(03)00504-5 Occurrence Handle14555227 Occurrence Handle1:CAS:528:DC%2BD3sXnvVeqs74%3D

    Article  PubMed  CAS  Google Scholar 

  • TR Radabaugh HV Aposhian (2000) ArticleTitleEnzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase Chem Res Toxicol 13 26–30 Occurrence Handle10.1021/tx990115k Occurrence Handle10649963 Occurrence Handle1:CAS:528:DyaK1MXnvFWhu74%3D

    Article  PubMed  CAS  Google Scholar 

  • PG Richman A Meister (1975) ArticleTitleRegulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione J Biol Chem 250 1422–1426 Occurrence Handle1112810 Occurrence Handle1:CAS:528:DyaE2MXhtlCktLw%3D

    PubMed  CAS  Google Scholar 

  • JN Sampayo A Olsen GJ Lithgow (2003) ArticleTitleOxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics Aging Cell 2 319–326 Occurrence Handle10.1046/j.1474-9728.2003.00063.x Occurrence Handle14677634 Occurrence Handle1:CAS:528:DC%2BD3sXpvV2gu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • M Schuliga S Chouchane ET Snow (2002) ArticleTitleUpregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethal concentrations of inorganic arsenic Toxicol Sci 70 183–192 Occurrence Handle10.1093/toxsci/70.2.183 Occurrence Handle12441363 Occurrence Handle1:CAS:528:DC%2BD38XptFOqsr0%3D

    Article  PubMed  CAS  Google Scholar 

  • N Scott KM Hatlelid NE MacKenzie DE Carter (1993) ArticleTitleReaction of arsenic(III) and arsenic(V) species with glutathione Chem Res Toxicol 6 102–106 Occurrence Handle10.1021/tx00031a016 Occurrence Handle8448339 Occurrence Handle1:CAS:528:DyaK3sXpsFOrtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Shimizu JF Hochadel BA Fulmer MP Waalkes (1998) ArticleTitleEffect of glutathione depletion and metallothionein gene expression on arsenic-induced cytotoxicity and c-myc expression in vitro Toxicol Sci 45 204–211 Occurrence Handle10.1006/toxs.1998.2539 Occurrence Handle9848127 Occurrence Handle1:CAS:528:DyaK1cXntlKmsLg%3D

    Article  PubMed  CAS  Google Scholar 

  • EG Stringham D Jones EP Candido (1992) ArticleTitleExpression of the polyubiquitin-encoding gene (ubq-1) in transgenic Caenorhabditis elegans Gene 113 165–173 Occurrence Handle10.1016/0378-1119(92)90392-3 Occurrence Handle1315299 Occurrence Handle1:CAS:528:DyaK38XktVaitrk%3D

    Article  PubMed  CAS  Google Scholar 

  • WN Tawe ML Eschbach RD Walter K Henkle-Duhrsen (1998) ArticleTitleIdentification of stress-responsive genes in Caenorhabditis elegans using RT-PCR differential display Nucleic Acids Res 26 1621–1627 Occurrence Handle10.1093/nar/26.7.1621 Occurrence Handle9512531 Occurrence Handle1:CAS:528:DyaK1cXis1OjtLk%3D

    Article  PubMed  CAS  Google Scholar 

  • PB Tchounwou BA Wilson A Ishaque (1999) ArticleTitleImportant considerations in the development of public health advisories for arsenic and arsenic containing compounds in drinking water Rev Environ Health 14 1–19

    Google Scholar 

  • PL Williams DB Dusenbery (1990) ArticleTitleAquatic toxicity testing using the nematode Caenorhabditis elegans Environ Toxicol Chem 9 1285–1290 Occurrence Handle1:CAS:528:DyaK3cXmt1Grtb4%3D

    CAS  Google Scholar 

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  1. Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 106, Taiwan

    Vivian Hsiu-Chuan Liao & Chan-Wei Yu

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  1. Vivian Hsiu-Chuan Liao
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Correspondence to Vivian Hsiu-Chuan Liao.

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Liao, V.HC., Yu, CW. Caenorhabditis elegans gcs-1 Confers Resistance to Arsenic-Induced Oxidative Stress. Biometals 18, 519–528 (2005). https://doi.org/10.1007/s10534-005-2996-3

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