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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Cell death induced by the Alternaria mycotoxin Alternariol
Fatma Bensassi1, Cindy Gallerne, Ossama Sharaf El Dein
1Laboratory for Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
Abstract:
Mycotoxins are unavoidable contaminants of most foods and feeds, and some are known to be detrimental to human health. It is thus worthwhile to understand how cells of the intestinal system, one of the primary targets of these toxins, respond to their toxic effects. In this study, human colon carcinoma cells were used to elucidate the cell death mode and the pathways triggered by Alternariol (AOH), the most important mycotoxin produced by Alternaria species, which are the most common mycoflora infecting small grain cereals worldwide. Treatment of cells with AOH resulted in a loss of cell viability by inducing apoptosis. AOH-induced apoptosis was mediated through a mitochondria-dependent pathway, characterized by a p53 activation, an opening of the mitochondrial permeability transition pore (PTP), a loss of mitochondrial transmembrane potential (ΔΨm), a downstream generation of O(2)(*-) and caspase 9 and 3 activation. Besides, deficiency of the pro-apoptotic protein Bax partially protected cells against AOH-induced mitochondrial alterations. In addition, experiments performed on purified mitochondria indicated that AOH does not directly target this organelle to induce cell death. Our results demonstrate for the first time that AOH-induced cytotoxicity is mediated by activation of the mitochondrial pathway of apoptosis in human colon carcinoma cells.
Insights
Alternariol (AOH), a common mycotoxin, triggers programmed cell death (apoptosis) in human colon cells. This occurs via a mitochondria-dependent pathway, highlighting AOH
Area of Science:
- Cell Biology
- Toxicology
- Molecular Biology
Background:
- Mycotoxins are prevalent food contaminants with known health risks.
- The intestinal system is a primary target for mycotoxin toxicity.
- Alternariol (AOH) is a significant mycotoxin from Alternaria species, common in cereals.
Purpose of the Study:
- To investigate the cell death mechanisms induced by Alternariol (AOH) in human colon carcinoma cells.
- To elucidate the specific pathways involved in AOH-induced cytotoxicity.
- To understand the role of mitochondria in AOH toxicity.
Main Methods:
- Human colon carcinoma cells were treated with AOH.
- Apoptosis induction and cell viability were assessed.
- Mitochondrial pathway activation markers (p53, PTP, ΔΨm, ROS, caspases) were analyzed.
- Experiments were conducted on purified mitochondria and Bax-deficient cells.
Main Results:
- AOH treatment led to apoptosis and loss of cell viability.
- AOH-induced apoptosis involved p53 activation and mitochondrial pathway signaling.
- Key events included PTP opening, loss of ΔΨm, ROS generation, and caspase activation.
- Bax deficiency offered partial protection against AOH-induced mitochondrial damage.
- AOH did not directly damage isolated mitochondria.
Conclusions:
- AOH induces cytotoxicity in human colon cells through apoptosis.
- The mitochondrial pathway is central to AOH-induced cell death.
- These findings provide novel insights into the toxicological effects of AOH on intestinal cells.
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