Abstract
This study evaluated the protective effect of proanthocyanidins (PCs) on reducing apoptosis in the mouse intestinal epithelial cell model MODE-K exposed to zearalenone (ZEA) through inhibition of the endoplasmic reticulum stress (ERS)-induced apoptosis pathway. Our results showed that PCs could reduce the rate of apoptosis in MODE-K cells exposed to ZEA (p < 0.01). PCs significantly increased the ZEA-induced antioxidant protective effects on the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on the content of GSH. PCs also significantly decreased the ZEA-induced increase in the content of malondialdehyde (MDA). The analysis indicated that ZEA increased both mRNA and protein expression levels of C/EBP homologous protein (CHOP), GRP78, c-Jun N-terminal kinase (JNK), and cysteinyl aspartate specific proteinase 12 (caspase-12) (p < 0.05), which are related to the ERS-induced apoptosis pathway. ZEA decreased levels of the pro-apoptotic related protein Bcl-2 (p < 0.05) and increased the anti-apoptotic related protein Bax (p < 0.05). Co-treatment with PCs was also shown to significantly reverse the expression levels of these proteins in MODE-K cells. The results demonstrated that PCs could protect MODE-K cells from oxidative stress and apoptosis induced by ZEA. The underlying mechanism may be that PCs can alleviate apoptosis in mouse intestinal epithelial cells by inhibition of the ERS-induced apoptosis pathway.
Keywords:
apoptosis; endoplasmic reticulum stress; intestinal epithelial cells; mice; oxidative damage; proanthocyanidins; zearalenone.
MeSH terms
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Animals
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Antioxidants / pharmacology*
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Apoptosis / drug effects
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Caspase 12 / genetics
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Caspase 12 / metabolism
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Cell Line
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Cell Survival / drug effects
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Endoplasmic Reticulum Chaperone BiP
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Endoplasmic Reticulum Stress / drug effects*
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Epithelial Cells / cytology
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Estrogens, Non-Steroidal / antagonists & inhibitors*
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Estrogens, Non-Steroidal / pharmacology
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Gene Expression Regulation / drug effects
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Glutathione / agonists
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Glutathione / antagonists & inhibitors
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Glutathione / metabolism
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Glutathione Peroxidase / genetics
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Glutathione Peroxidase / metabolism
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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Intestine, Small / cytology
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Intestine, Small / drug effects
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Intestine, Small / metabolism
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Malondialdehyde / agonists
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Malondialdehyde / antagonists & inhibitors
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Malondialdehyde / metabolism
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Mice
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Proanthocyanidins / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
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Transcription Factor CHOP / genetics
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Transcription Factor CHOP / metabolism
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Zearalenone / antagonists & inhibitors*
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Zearalenone / pharmacology
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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Antioxidants
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Bax protein, mouse
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Ddit3 protein, mouse
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Endoplasmic Reticulum Chaperone BiP
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Estrogens, Non-Steroidal
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Heat-Shock Proteins
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Hspa5 protein, mouse
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Proanthocyanidins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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Bcl2 protein, mouse
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Transcription Factor CHOP
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Malondialdehyde
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Zearalenone
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Glutathione Peroxidase
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Superoxide Dismutase
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JNK Mitogen-Activated Protein Kinases
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Casp12 protein, mouse
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Caspase 12
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Glutathione