title: RNA-Seq Reveals Acute Manganese Exposure Increases Endoplasmic Reticulum Related and Lipocalin mRNAs in Caenorhabditis elegans.
abstract: Manganese (Mn) is an essential nutrient; nonetheless, excessive amounts can accumulate in brain tissues causing manganism, a severe neurological condition. Previous studies have suggested oxidative stress, mitochondria dysfunction, and impaired metabolism pathways as routes for Mn toxicity. Here, we used the nematode Caenorhabditis elegans to analyze gene expression changes after acute Mn exposure using RNA-Seq. L1 stage animals were exposed to 50 mM MnCl2 for 30 min and analyzed at L4. We identified 746 up- and 1828 downregulated genes (FDR corrected p < 0.05; two-fold change) that included endoplasmic reticulum related abu and fkb family genes, as well as six of seven lipocalin-related (lpr) family members. These were also verified by qRT-PCR. RNA interference of lpr-5 showed a dramatic increase in whole body vulnerability to Mn exposure. Our studies demonstrate that Mn exposure alters gene transcriptional levels in different cell stress pathways that may ultimately contribute to its toxic effects.
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio 70211, Finland.
authors.forename: Martina
authors.initials: M
authors.lastname: Rudgalvyte
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio 70211, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio 70211, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Lakso
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Nass
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio 70211, Finland. GarryGWong@umac.mo.|Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau S.A.R., 999078, China. GarryGWong@umac.mo.
authors.forename: Garry
authors.initials: G
authors.lastname: Wong
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008345:Manganese / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017423:Sequence Analysis, RNA
chemical_list: D054834:Lipocalins; D012333:RNA, Messenger; D008345:Manganese
keywords: Heavy Metal; Model Organism; Next-Generation Sequencing; RNAi; Transcriptomics