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Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells.
Redox Biol. 75:103290 (2024)
Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2). The results reveal a synergistic effect of Co and Ni, leading to significantly higher number of differentially expressed genes (DEGs) compared to individual exposure. There was a clear enrichment of Nrf2 regulated genes linked to pathways such as glycolysis, iron and glutathione metabolism, and sphingolipid metabolism, confirmed by targeted analysis. Co and Ni exposure alone and combined caused nuclear Nrf2 translocation, while only combined exposure significantly affects iron and glutathione metabolism, evidenced by upregulation of HMOX-1 and iron storage protein FTL. Both metals impact sphingolipid metabolism, increasing dihydroceramide levels and decreasing ceramides, sphingosine and lactosylceramides, along with diacylglycerol accumulation. By combining transcriptomics and analytical methods, this study provides valuable insights into molecular mechanisms of Co and Ni toxicity, paving the way for further understanding of metal stress.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cobalt ; Metal Interactions ; Nickel ; Nrf2 Signaling ; Sphingolipid Metabolism ; Transcriptomic Analysis; Stem-cells; Hypoxia; Cancer; Metabolism; Autophagy; Chloride; Talk; Gene
ISSN (print) / ISBN
2213-2317
e-ISSN
2213-2317
Zeitschrift
Redox Biology
Quellenangaben
Band: 75,
Artikelnummer: 103290
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Analytical BioGeoChemistry (BGC)
Förderungen
DFG Research Infrastructure NGS_CC as part of the Next Generation Sequencing Competence Network
University of Wuppertal and the Faculty of Mathematics and Natural Sciences
DFG Research Unit TraceAge (FOR 2558)
University of Wuppertal and the Faculty of Mathematics and Natural Sciences
DFG Research Unit TraceAge (FOR 2558)