RNA-Seq Reveals Acute Manganese Exposure Increases Endoplasmic Reticulum Related and Lipocalin mRNAs in Caenorhabditis elegans

Martina Rudgalvyte, Juhani Peltonen, Merja Lakso, Richard Nass, Garry Wong

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalJournal of Biochemical and Molecular Toxicology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2016

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Keywords

  • Heavy metal
  • Model organism
  • Next-generation sequencing
  • RNAi
  • Transcriptomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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