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Activation of mitogen-activated protein kinase by the carcinogenic mycotoxin fumonisin B1
E V Wattenberg1, F A Badria, W T Shier
1Division of Environmental and Occupational Health, University of Minnesota, Minneapolis 55455, USA. evwatt@mail.eoh.umn.edu
Abstract:
Recent studies indicate that the mycotoxin and putative carcinogen fumonisin B1 stimulates mitogenesis in Swiss 3T3 fibroblasts. Because mitogen-activated protein kinase (MAPK) is a key enzyme in the signal transduction pathways activated by many mitogens, we hypothesized that fumonisin B1 might modulate MAPK activity. Consistent with other reports, we observed that fumonisin B1 is synergistic with insulin for mitogenesis in Swiss 3T3 cells. We also observed that: (1) fumonisin B1 stimulates rapid, transient activation of MAPK; and (2) the dose-response curve for fumonisin B1-stimulated activation of MAPK is similar to the dose-response curve for the mitogenic effects of fumonisin B1. In contrast to fumonisin B1, insulin stimulates minimal activation of MAPK in Swiss 3T3 cells. The observation that fumonisin B1 and insulin differ with respect to the modulation of MAPK activity suggests a possible mechanism for their synergistic stimulation of mitogenesis in Swiss 3T3 cells.
Insights
The mycotoxin fumonisin B1 activates mitogen-activated protein kinase (MAPK) and stimulates cell growth in Swiss 3T3 fibroblasts. This MAPK activation may explain how fumonisin B1 and insulin work together to promote cell proliferation.
Area of Science:
- Cell Biology
- Toxicology
- Biochemistry
Background:
- Fumonisin B1 is a mycotoxin and potential carcinogen.
- Mitogenesis, the process of cell proliferation, is stimulated by various signaling pathways.
- Mitogen-activated protein kinase (MAPK) is a crucial enzyme in signal transduction pathways activated by mitogens.
Purpose of the Study:
- To investigate the effect of fumonisin B1 on MAPK activity in Swiss 3T3 fibroblasts.
- To determine if fumonisin B1 modulates MAPK activity, a key enzyme in mitogenic signaling.
- To explore the relationship between fumonisin B1-induced MAPK activation and its mitogenic effects.
Main Methods:
- Utilizing Swiss 3T3 fibroblasts as a model system.
- Treating cells with fumonisin B1 and insulin to assess mitogenesis.
- Measuring MAPK activity in response to fumonisin B1 and insulin exposure.
- Comparing dose-response curves for fumonisin B1's mitogenic effects and MAPK activation.
Main Results:
- Fumonisin B1 synergizes with insulin to stimulate mitogenesis in Swiss 3T3 cells.
- Fumonisin B1 rapidly and transiently activates MAPK.
- The dose-response for fumonisin B1-induced MAPK activation mirrors its mitogenic dose-response.
- Insulin alone elicits minimal MAPK activation in these cells.
Conclusions:
- Fumonisin B1 activates MAPK, suggesting a role in mitogenic signaling.
- Differences in MAPK activation between fumonisin B1 and insulin may explain their synergistic mitogenic effect.
- MAPK signaling is a potential mechanism underlying fumonisin B1's proliferative effects.