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Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.

ABSTRACT: Methylmercury (MeHg) is a persistent environmental and dietary contaminant that causes serious adverse developmental and physiologic effects at multiple cellular levels. In order to understand more fully the consequences of MeHg exposure at the molecular level, we profiled gene and miRNA transcripts from the model organism Caenorhabditis elegans. Animals were exposed to MeHg (10 ?M) from embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the Illumina platform revealed 541 genes up- and 261 genes down-regulated at a cutoff of 2-fold change and false discovery rate-corrected significance q < 0.05. Among the up-regulated genes were those previously shown to increase under oxidative stress conditions including hsp-16.11 (2.5-fold), gst-35 (10.1-fold), and fmo-2 (58.5-fold). In addition, we observed up-regulation of 6 out of 7 lipocalin related (lpr) family genes and down regulation of 7 out of 15 activated in blocked unfolded protein response (abu) genes. Gene Ontology enrichment analysis highlighted the effect of genes related to development and organism growth. miRNA-seq analysis revealed 6-8 fold down regulation of mir-37-3p, mir-41-5p, mir-70-3p, and mir-75-3p. Our results demonstrate the effects of MeHg on specific transcripts encoding proteins in oxidative stress responses and in ER stress pathways. Pending confirmation of these transcript changes at protein levels, their association and dissociation characteristics with interaction partners, and integration of these signals, these findings indicate broad and dynamic mechanisms by which MeHg exerts its harmful effects.

SUBMITTER: Rudgalvyte M

PROVIDER: S-EPMC3816353 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.

Rudgalvyte Martina M VanDuyn Natalia N Aarnio Vuokko V Heikkinen Liisa L Peltonen Juhani J Lakso Merja M Nass Richard R Wong Garry G

Toxicology letters 20130718 2

Methylmercury (MeHg) is a persistent environmental and dietary contaminant that causes serious adverse developmental and physiologic effects at multiple cellular levels. In order to understand more fully the consequences of MeHg exposure at the molecular level, we profiled gene and miRNA transcripts from the model organism Caenorhabditis elegans. Animals were exposed to MeHg (10 μM) from embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the Illumina platform revealed 541 ...[more]

PMID: 23872261

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Project description:The neurotransmitter dopamine is a neuromodulator in the positive and negative regulation of brain circuits. Dopamine insufficiency or overload has been implicated in aberrant activities of neural circuits that play key roles in the pathogenesis of neurological and psychiatric diseases. Dopaminergic neurons are vulnerable to environmental insults. The neurotoxin methylmercury (MeHg) produces dopaminergic neuron damage in rodent as well as in Caenorhabditis elegans (C. elegans) models. Previous studies have demonstrated the utility of C. elegans as an alternative and complementary experimental model in dissecting out mechanism of MeHg-induced dopaminergic neurodegeneration. However, a sensitive pathological change that marks early events in neurodegeneration induced by environmental level of MeHg, is still lacking. By establishing a chronic exposure C. elegans model, for the first time, we have shown the propensity of MeHg (5 μM, 10 days) to induce bright puncta of dat-1::mCherry aggreagtes in the dendrites of cephalic (2 CEPs) dopaminergic neurons in a dose- and time-dependent manner, while these changes were not found in other dopaminergic neurons: anterior deirids (2 ADEs) and posterior deirids (2 PDEs), cholinergic neurons (2 AIYs) or glutamatergic neurons (2 PVDs). The bright puncta appear as an aggregation of mCherry proteins accumulating in dendrites. Further staining shows that the puncta were not inclusions in lysosome, or amyloid protein aggregates. In addition, features of the puncta including enlarged sphere shape (0.5-2 μm diameters), bright and accompanying with the shrinkage of the dendrite suggest that the puncta are likely composed of homologous mCherry molecules packaged at the dendritic site for exportation. Moreover, in the glutathione S-transferase 4 (gst-4) transcriptional reporter strain and RT-PCR assay, the expression levels of gst-4 and tubulins (tba-1 and tba-2) genes were not significantly modified under this chronic exposure paradigm, but gst-4 did show significant changes in an one day exposure paradigm. Collectively, these results suggest that CEP dopaminergic neurons are a sensitive target of MeHg, and the current exposure paradigm could be used as a model to investigate mechanism of dopaminergic neurotoxicity.

Dataset Information

Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.

Publications

Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.

Similar Datasets

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