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

6533b822fe1ef96bd127d99a

RESEARCH PRODUCT

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

Lara Manyes Danyel Jennen Florian Caiment Laura Escrivá

subject

0301 basic medicine Programmed cell death CYTOCHROME-C RELEASE BCL-2 FAMILY Cell Membrane Permeability Respiratory chain Cell Culture Techniques CASPASE-3 ACTIVATION Apoptosis Oxidative phosphorylation CHO-K1 CELLS Toxicology Jurkat cells Oxidative Phosphorylation Electron Transport 03 medical and health sciences Jurkat Cells FUSARIUM MYCOTOXINS Immunotoxicology Depsipeptides Humans REAL-TIME PCR OXIDATIVE STRESS Transcriptomics Caspase INDUCED APOPTOSIS LEUKEMIA-CELLS 030102 biochemistry & molecular biology biology Dose-Response Relationship Drug Chemistry Jurkat Gene Expression Profiling Bcl-2 family DEATH General Medicine Beauvericin Toxicogenomics Cell biology Gene expression profiling 030104 developmental biology Mitochondrial respiratory chain Gene Ontology biology.protein RNA-seq Transcriptome

description

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.

year	journal	country	edition	language
2018-03-01	Toxicology Letters

10.1016/j.toxlet.2017.11.035 https://doi.org/10.1016/j.toxlet.2017.11.035