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Deoxynivalenol induces apoptosis in PC12 cells via the mitochondrial pathway
Xichun Wang1, Wei Xu1, Mengxue Fan1
1College of Animal Science and Technology, Anhui Agricultural University, 130 West Changjiang Road, Hefei 230036, China.
Abstract:
Deoxynivalenol (DON) has broad toxicity in animals and humans. In this study the impact of DON treatment on apoptotic pathways in PC12 cells was determined. The effects of DON were evaluated on (i) typical indicators of apoptosis, including cellular morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio in PC12 cells, and on (ii) the expression of key genes and proteins related to apoptosis, including Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3. DON treatment inhibited proliferation of PC12 cells, induced significant morphological changes and apoptosis, promoted the release of Cyt C and AIF from the mitochondria, and increased the activities of cleaved-Caspase9 and cleaved-Caspase3. Bcl-2 expression decreased with increasing DON concentrations, in contrast to Bax and Bid, which were increased with increasing DON concentration. These data demonstrate that DON induces apoptosis in PC12 cells through the mitochondrial apoptosis pathway.
Insights
Deoxynivalenol (DON) triggers cell death in PC12 cells by activating the mitochondrial apoptosis pathway. This mycotoxin disrupts cell integrity and key protein expressions, leading to programmed cell death.
Area of Science:
- Toxicology
- Cell Biology
- Molecular Biology
Background:
- Deoxynivalenol (DON) is a prevalent mycotoxin with known toxicity to animals and humans.
- Understanding DON's cellular mechanisms is crucial for assessing its health risks.
Purpose of the Study:
- To investigate the impact of Deoxynivalenol (DON) on apoptotic pathways in PC12 cells.
- To analyze DON's effects on cellular morphology, viability, and apoptosis markers.
- To examine the expression of key apoptosis-related genes and proteins.
Main Methods:
- PC12 cells were treated with varying concentrations of DON.
- Evaluated typical apoptosis indicators: morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio.
- Assessed the expression of apoptosis-related genes/proteins: Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis-inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3.
Main Results:
- DON inhibited PC12 cell proliferation and induced significant morphological changes and apoptosis.
- DON promoted the release of cytochrome C (Cyt C) and apoptosis-inducing factor (AIF) from mitochondria.
- DON increased cleaved-Caspase9 and cleaved-Caspase3 activities, decreased Bcl-2, and increased Bax and Bid expression.
Conclusions:
- Deoxynivalenol (DON) induces apoptosis in PC12 cells.
- The mechanism involves the activation of the mitochondrial apoptosis pathway.
- DON alters the expression of critical proteins regulating apoptosis.
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