Journal
APPLIED SCIENCES-BASEL
Volume 11, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/app11062678
Keywords
gene expression; lipid peroxides; Caco-2 cells
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The study revealed that treatment with 13-HPODE induced the expression of genes related to detoxification and metabolic pathways in PDiff Caco-2 cells, while downregulating some proliferation-related genes. Additionally, 13-HPODE was found to impact ribosome biogenesis, phagosome, and mitochondrial function, potentially contributing to disease development or progression.
Dietary lipid peroxides (LOOHs) have been linked to gut pathologies including inflammatory bowel disease and cancer. As poorly differentiated (PDiff) intestinal epithelial (Caco-2) cells represent tumor cells and could model intestinal crypt cells, we investigated the cellular response of PDiff Caco-2 cells to the most common dietary LOOH, 13-hydroperoxyoctadecadienoic acid (13-HPODE), using RNA sequencing (RNA-seq). Further, we compared the results with the transcriptomic profiles of PDiff cells exposed to linoleic acid (LA) or hydrogen peroxide (H2O2). The results showed that 13-HPODE treatment induces expression of genes related to detoxification and several metabolic pathways including glycogen and amino acid metabolism, which may create a tumorigenic environment despite the downregulation of some proliferation-related genes. 13-HPODE also enhanced peroxisome proliferator-activated receptor signaling involved in lipid metabolism, homeostasis, and inflammation. Additionally, results indicated that 13-HPODE impacts ribosome biogenesis, phagosome, and mitochondrial function through disrupted electron transport chain, which may contribute to disease development or progression. RNA-seq results were validated using qRT-PCR. This study provides an understanding of PDiff Caco-2 cell response to 13-HPODE and the mechanisms by which 13-HPODE modulates cellular processes that may contribute to disease development or progression.
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