Theonellamide F, a Bicyclic Peptide Marine Toxin, Induces Formation of Vacuoles in 3Y1 Rat Embryonic Fibroblast
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Published on: June 28, 2019
1Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo 113-8657, Japan
Abstract:
: The effect of a marine bicyclic peptide, theonellamide F, on vacuole formation in exponentially growing 3Y1 rat embryonic fibroblasts was studied in comparison with the effect of monensin. Many abnormally large vacuoles appeared around the nucleus in the cells treated with 6 µM theonellamide F within 24 hours. Following prolonged treatment with this agent, the number of enlarged vacuoles increased. Such vacuoles accumulated many granules that showed Brownian movement. The effect of theonellamide F on the cells was more drastic in an amino-acid-deficient medium, in which all cells died within 1 hour at a 3-µM concentration of the agent. Theonellamide F probably affects cellular autophagy, inhibiting the degradation of the organelles and turnover of proteins. Monensin, a well-known Na(+) ionophore that disintegrates the Golgi apparatus, induced similar types of vacuole formation, although the vacuoles were localized in a region slightly distant from the nucleus. Monensin readily affected cell morphology, resulting in cell death. We propose that theonellamide F, like monensin, is a useful agent for investigating membrane structures in cells.
Insights
The marine peptide theonellamide F induces large vacuole formation in rat cells, potentially by affecting autophagy. This compound, similar to monensin, shows promise for studying cellular membrane structures.
Area of Science:
- Marine natural products
- Cell biology
- Biochemistry
Background:
- Vacuole formation is a critical cellular process.
- Marine-derived compounds offer unique biological activities.
- Theonellamide F is a marine bicyclic peptide with unknown cellular effects.
Purpose of the Study:
- To investigate the effect of theonellamide F on vacuole formation in 3Y1 rat embryonic fibroblasts.
- To compare the vacuolating effects of theonellamide F with monensin.
- To explore the potential mechanism of action of theonellamide F.
Main Methods:
- Treatment of 3Y1 rat embryonic fibroblasts with theonellamide F and monensin.
- Microscopic observation of vacuole formation and cellular morphology.
- Culturing cells in amino-acid-deficient medium to assess toxicity.
Main Results:
- Theonellamide F induced the formation of abnormally large vacuoles around the nucleus in a dose-dependent manner.
- Prolonged exposure to theonellamide F increased vacuole accumulation, with granules exhibiting Brownian movement.
- Theonellamide F exhibited drastic cytotoxicity in amino-acid-deficient medium, causing rapid cell death.
- Monensin induced similar vacuole formation but with different localization and also caused cell death.
Conclusions:
- Theonellamide F likely interferes with cellular autophagy, inhibiting organelle degradation and protein turnover.
- Theonellamide F and monensin are comparable agents for studying cellular membrane dynamics and vacuole formation.
- Further research into theonellamide F could provide insights into membrane structure and cellular processes.
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