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Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells.
Carta, Giada; van der Stel, Wanda; Scuric, Emma W J; Capinha, Liliana; Delp, Johannes; Bennekou, Susanne Hougaard; Forsby, Anna; Walker, Paul; Leist, Marcel; van de Water, Bob; Jennings, Paul.
Affiliation
  • Carta G; Division of Molecular and Computational Toxicology, Vrije University Amsterdam, Amsterdam, the Netherlands. g.carta@vu.nl.
  • van der Stel W; Division of Drug Discovery and Safety, Leiden Academic Centre of Drug Research, Leiden University, Leiden, the Netherlands.
  • Scuric EWJ; Division of Molecular and Computational Toxicology, Vrije University Amsterdam, Amsterdam, the Netherlands.
  • Capinha L; Division of Molecular and Computational Toxicology, Vrije University Amsterdam, Amsterdam, the Netherlands.
  • Delp J; In Vitro Toxicology and Biomedicine, Department inaugurated by the Doerenkamp­Zbinden Foundation, University of Konstanz, Konstanz, Germany.
  • Bennekou SH; Section for Advice, Danish Patient Safety Authority, Randers, Denmark.
  • Forsby A; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
  • Walker P; Cyprotex Discovery Ltd., Alderley Park, Macclesfield, Cheshire, UK.
  • Leist M; In Vitro Toxicology and Biomedicine, Department inaugurated by the Doerenkamp­Zbinden Foundation, University of Konstanz, Konstanz, Germany.
  • van de Water B; Division of Drug Discovery and Safety, Leiden Academic Centre of Drug Research, Leiden University, Leiden, the Netherlands.
  • Jennings P; Division of Molecular and Computational Toxicology, Vrije University Amsterdam, Amsterdam, the Netherlands.
Cell Biol Toxicol ; 39(6): 3031-3059, 2023 12.
Article in En | MEDLINE | ID: mdl-37353587
ABSTRACT
Analysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound's toxic mode of action, by revealing specific pathway activation and other transcriptional modulations. Mapping changes in cellular behaviour to chemical insult, facilitates the characterisation of chemical hazard. In this study, we assessed the transcriptional landscape of mitochondrial impairment through the inhibition of the electron transport chain (ETC) in a human renal proximal tubular cell line (RPTEC/TERT1). We identified the unfolded protein response pathway (UPR), particularly the PERK/ATF4 branch as a common cellular response across ETC I, II and III inhibitions. This finding and the specific genes elaborated may aid the identification of mitochondrial liabilities of chemicals in both legacy data and prospective transcriptomic studies.
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Full text: 1 Database: MEDLINE Main subject: Epithelial Cells / Kidney Type of study: Prognostic_studies Limits: Humans Language: En Year: 2023 Type: Article
Fulltext
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Epithelial Cells / Kidney Type of study: Prognostic_studies Limits: Humans Language: En Year: 2023 Type: Article