Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells

L. Escriva*, D. Jennen, F. Caiment, L. Manyes

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 mu M; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cellular respiration significantly altered. Molecular functions linked to mitochondrial respiratory chain and oxidoreductase activity were over-represented (q-value < 0.01). Pathway analysis revealed oxidative phosphorylation and electron transport chain as the most significantly altered pathways in all studied doses (z-score > 1.96; adj p-value < 0.05). 77 genes involved in the respiratory chain were significantly down-regulated at least at one dose. Moreover, 21 genes related to apoptosis and programmed cell death, and 12 genes related to caspase activity were significantly altered, mainly affecting initiator caspases 8, 9 and 10. The results demonstrated BEA-induced mitochondrial damage affecting the respiratory chain, and pointing to apoptosis through the caspase cascade in human lymphoblastic T cells.
Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalToxicology Letters
Volume284
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Beauvericin
  • Jurkat
  • Immunotoxicology
  • RNA-seq
  • Toxicogenomics
  • Transcriptomics
  • CYTOCHROME-C RELEASE
  • REAL-TIME PCR
  • CASPASE-3 ACTIVATION
  • FUSARIUM MYCOTOXINS
  • INDUCED APOPTOSIS
  • OXIDATIVE STRESS
  • LEUKEMIA-CELLS
  • CHO-K1 CELLS
  • BCL-2 FAMILY
  • DEATH

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