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Toxicogenomic responses of C. elegans to gold nanoparticles

ABSTRACT: We used Au nanoparticles (Au-NPs) as a model for studying particle specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, free living nematode Caenorhabditis elegans. Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC10 (5.9 mg L-1) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Activation of 26 pqn/abu genes from noncanonical Unfolded Protein Response (UPR) pathway and up-regulation of molecular chaperones (hsp-16.1, hsp-70, hsp-3 and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Inhibition of abu-11 with RNAi showed increase in mortality in Au-NP exposed nematodes suggesting possible involvement of abu-11 (a gene associated with specific to C. elegans UPR) in a protective mechanism against Au-NPs. Exposure to Au-NPs also caused activation of genes involved in apoptosis and necrosis and resulted ultimately in 10% mortality. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to a model ecoreceptor which activate both general and specific biological pathways.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE32521 | GEO | 2012/04/16

SECONDARY ACCESSION(S): PRJNA147847

REPOSITORIES: GEO

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Toxicogenomic responses of C. elegans to gold nanoparticles

Project description:We used Au nanoparticles (Au-NPs) as a model for studying particle specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, free living nematode Caenorhabditis elegans. Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC10 (5.9 mg L-1) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Activation of 26 pqn/abu genes from noncanonical Unfolded Protein Response (UPR) pathway and up-regulation of molecular chaperones (hsp-16.1, hsp-70, hsp-3 and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Inhibition of abu-11 with RNAi showed increase in mortality in Au-NP exposed nematodes suggesting possible involvement of abu-11 (a gene associated with specific to C. elegans UPR) in a protective mechanism against Au-NPs. Exposure to Au-NPs also caused activation of genes involved in apoptosis and necrosis and resulted ultimately in 10% mortality. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to a model ecoreceptor which activate both general and specific biological pathways. Age-synchronized L3 nematodes (about 2000 nematodes per replicate with 3 replicates per treatment) were exposed to LC10 (5.9 mgL-1 ) of 4-nm citrate-coated Au-NP using 6 cm petri-dishes with 4 ml of exposure solution per dish. The N2 nematodes at L3 stageused were used and they were exposed in 50% K-Medium (31.68 mM KCl, 51.37 mM NaCl) for 12h. At 12 h all solutions were replaced with 50% K-Medium and left for another 12 h. After 24 h RNA was extracted from each of the replicates .

2012-04-15 | E-GEOD-32521 | biostudies-arrayexpress

A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

Project description:Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. This SuperSeries is composed of the SubSeries listed below.

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A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

Project description:This SuperSeries is composed of the following subset Series: GSE4093: Resveratrol treatment of daf-16 mutant C. elegans GSE4094: N2 worms treated with Resveratrol GSE4095: Sir-2.1 low copy transgenic Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. Refer to individual Series

2006-03-07 | E-GEOD-4402 | biostudies-arrayexpress

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Project description:Gold nanoparticles (Au NPs) are uniquely suited for various biomedical applications due to the combination of their optical properties with their easily functionalized surfaces. The Au NP surface can be tailored to improve biocompatibility while also attaching targeting ligands or drugs. However, information on how these tailored surface chemistries may affect cell gene expression is scarce. Using two model human cells line, human dermal fibroblasts and prostate cancer cells, microarray experiments measured gene expression over 27,000 human genes. Each of the cell lines was exposed to four related types of surface-modified Au NPs at two different concentrations, and the microarray data was analyzed by weighted gene correlation network analysis and gene functional annotation. Au NPs were shown to affect genes associated with a variety of cellular functions, and surface charge and chemistry were linked with the types of parthways changed and the degree of which those changes occured.

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Exposure of C. elegans to AOBr-containing surface water samples and to a M. aeruginosa batch culture

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2015-05-12 | E-GEOD-68709 | biostudies-arrayexpress

Exposure of C. elegans to AOBr-containing surface water samples and to a M. aeruginosa batch culture

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