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Viability Assays for Cells in Culture
Published on: January 20, 2014
Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines
Helene Stockmann-Juvala1, Jonne Naarala, Jarkko Loikkanen
1Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland. helene.stockmann-juvala@ttl.fi
Abstract:
Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticilliodes, which commonly infects corn across the world. Fusarium fungi may also be found in moisture-damaged buildings. In this study, we investigated the role of apoptosis in the toxicity of FB(1) in four different cell lines. Activation of caspase-3-like protease, DNA fragmentation and expression of p53 and Bcl-2 family proteins were studied in mouse GT1-7 hypothalamic, rat C6 glioblastoma, human U-118MG glioblastoma, and human SH-SY5Y neuroblastoma cells exposed to 0.1-100microM FB(1) for 0-144h. Caspase-3-like protease activity increased in all cell lines, except SH-SY5Y, at 48-144h, and internucleosomal DNA fragmentation occurred in all of the cell lines, pointing to a role for apoptosis in the toxicity of FB(1). However, the expressions of p53 or pro- or antiapoptotic Bcl-2 family proteins (Bax, Bcl-2, Bcl-X(L) and Mcl-1) were not affected in any of the cell lines even after prolonged exposure to FB(1) at high doses. The results of this study, together with the results of our previous studies, provide evidence that FB(1) is a potential neurotoxin, but that the toxicity of FB(1) varies between different cell lines. The sensitivity of these cell lines towards FB(1) is as follows: U-118MG>GT1-7>C6>SH-SY5Y cells. These results are consistent with the assumption that cells of glial origin may be more sensitive towards FB(1) than cells of neural origin.
Insights
Fumonisin B(1) (FB(1)), a mycotoxin from Fusarium, induces apoptosis in various cell lines, suggesting it is a potential neurotoxin. Its toxicity varies by cell type, with glial cells being more sensitive than neural cells.
Area of Science:
- Toxicology
- Cell Biology
- Mycotoxicology
Background:
- Fumonisin B(1) (FB(1)) is a prevalent mycotoxin produced by Fusarium verticilliodes, found in contaminated corn and moisture-damaged buildings.
- Understanding the cellular mechanisms of FB(1) toxicity is crucial due to its widespread occurrence and potential health implications.
Purpose of the Study:
- To investigate the role of apoptosis in Fumonisin B(1) toxicity across four distinct cell lines.
- To determine the differential sensitivity of various cell types to FB(1)-induced apoptosis.
Main Methods:
- Exposure of mouse GT1-7 hypothalamic, rat C6 glioblastoma, human U-118MG glioblastoma, and human SH-SY5Y neuroblastoma cells to FB(1) (0.1-100 microM) for 0-144 hours.
- Assessed caspase-3-like protease activity, DNA fragmentation, and expression of p53 and Bcl-2 family proteins.
Main Results:
- Apoptosis, indicated by increased caspase-3-like protease activity and DNA fragmentation, was observed in most cell lines (except SH-SY5Y for protease activity).
- Expressions of p53 and Bcl-2 family proteins remained unaffected by FB(1) exposure, even at high doses and prolonged durations.
- Cellular sensitivity to FB(1) followed the order: U-118MG > GT1-7 > C6 > SH-SY5Y, with glial cells showing higher sensitivity than neural cells.
Conclusions:
- FB(1) induces apoptosis in a cell-type-dependent manner, supporting its role as a potential neurotoxin.
- Glial-derived cells appear more susceptible to FB(1) toxicity compared to neural-derived cells.
- The lack of change in p53 and Bcl-2 family protein expression suggests alternative pathways mediate FB(1) toxicity.