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Analysis of fumonisin B1-induced apoptosis
C Jones1, J R Ciacci-Zanella, Y Zhang
1Center for Biotechnology, Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, East Campus Loop, Lincoln, Nebraska, USA.
Abstract:
Fumonisins are mycotoxins produced by Fusarium moniliforme, a prevalent fungus that infects corn and other cereal grains. Fumonisin B1(FB1 is the most common mycotoxin produced by F. moniliforme, suggesting it has toxicologic significance. The structure of FB1 resembles sphingoid bases, and it inhibits ceramide synthase. Because sphingoid bases regulate cell growth, differentiation, transformation, and apoptosis, it is not surprising to find that FB1 can alter growth of certain mammalian cells. Previous studies concluded FB1-induced apoptosis, or cell cycle arrest, in African green monkey kidney fibroblasts (CV-1). In this study we have identified genes that inhibit FB1 induced apoptosis in CV-1 cells and two mouse embryo fibroblasts (MEF). A baculovirus gene, inhibitor of apoptosis (CpIAP), protected these cells from apoptosis. CpIAP blocks apoptosis induced by the tumor necrosis factor (TNF) pathway as well as other mechanisms. Further support for the involvement of the TNF signal transduction pathway in FB1 induced apoptosis was the cleavage of caspase 8. Inhibition of caspases by the baculovirus gene (italic)p35 also inhibited FB1-induced apoptosis. The tumor suppressor gene p53 was not required for FB1 induced apoptosis because p53-/- MEF undergo apoptosis following FB1 treatment. Furthermore, Bcl-2 was not an effective inhibitor of FB1-induced apoptosis in CV-1 cells or p53+/+ MEF. In summary, these results provide new information to help understand the mechanism by which FB1 induces apoptosis.
Insights
Fumonisin B1 (FB1) triggers apoptosis in mammalian cells by inhibiting ceramide synthase. Specific genes, like CpIAP and p35, can block this FB1-induced cell death, offering insights into its toxicological mechanisms.
Area of Science:
- Toxicology
- Molecular Biology
- Cell Biology
Background:
- Fumonisins are mycotoxins from Fusarium moniliforme, commonly found in corn.
- Fumonisin B1 (FB1) is a prevalent mycotoxin with toxicological significance.
- FB1 structurally mimics sphingoid bases and inhibits ceramide synthase, impacting cell regulation.
Purpose of the Study:
- To identify genes that inhibit FB1-induced apoptosis in mammalian cells.
- To elucidate the molecular pathways involved in FB1-induced cell death.
Main Methods:
- Utilized African green monkey kidney fibroblasts (CV-1) and mouse embryo fibroblasts (MEF).
- Investigated the effects of baculovirus genes inhibitor of apoptosis (CpIAP) and p35 on FB1-induced apoptosis.
- Assessed the role of the tumor suppressor gene p53 and Bcl-2 in FB1-induced apoptosis.
Main Results:
- The baculovirus gene CpIAP protected CV-1 and MEF cells from FB1-induced apoptosis.
- CpIAP demonstrated inhibition of apoptosis via the tumor necrosis factor (TNF) pathway.
- Cleavage of caspase 8 and inhibition by p35 further supported TNF pathway involvement.
- p53 was not essential for FB1-induced apoptosis, as p53-/- MEF cells underwent apoptosis.
- Bcl-2 was ineffective in inhibiting FB1-induced apoptosis in tested cell lines.
Conclusions:
- FB1 induces apoptosis through mechanisms involving the TNF signaling pathway and caspase activation.
- Specific viral genes (CpIAP, p35) can counteract FB1-induced apoptosis.
- The p53 and Bcl-2 pathways are not the primary mediators of FB1-induced apoptosis.