Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake
- Author
- Bryan Gonzales (UGent) , Guy Smagghe (UGent) , Hanne Vissenaekens, Charlotte Grootaert (UGent) , Andreja Rajkovic (UGent) , Tom Van de Wiele (UGent) , Katleen Raes (UGent) and John Van Camp (UGent)
- Organization
- Abstract
- Scope: Intestinal cells are constantly exposed to luminal toxins. In this study, we investigated the effect of cellular stress caused by valinomycin, which is structurally and functionally similar to the bacterial toxin cereulide, on quercetin metabolism and cellular localization in undifferentiated cells. Methods and results: Coadministration of quercetin and valinomycin (50 mu M quercetin/0.05 mu M valinomycin) reduced intracellular reactive oxygen species content and increased cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) of Caco-2 cells compared to valinomycin-only (0.05 mu M) treatment. Quercertin was effectively metabolized into methyl, glucuronide, and sulfate conjugates, which were mostly secreted into to the culture medium. Three different O-methylated quercetin isomers were detected. Two were exported from the cells and one remained intracellularly. Further, valinomycin caused an increase in the intracellular accumulation of O-methylated quercetin metabolites compared to cells treated only with quercetin. In valinomycin-untreated cells, quercetin and O-methylated quercetin metabolite were localized in the cell membrane, whereas valinomycin treatment resulted in their uptake by the cells. Conclusion: This is the first report on the change in metabolism, localization, and accumulation of O-methylated quercetin metabolites in undifferentiated Caco-2 cells as a response during stress caused by valinomycin. These results indicate a potential cellular stress response mechanism in undifferentiated Caco-2 cells, which adds novel insights into the mechanisms of flavonoid cellular bioactivity.
- Keywords
- Metabolism, Caco-2, Methylquercetin, Quercetin, Valinomycin, ANTIOXIDANT ACTIVITY RELATIONSHIPS, CACO-2 CELLS, CAULIFLOWER WASTE, MASS-SPECTROMETRY, IN-VITRO, FLAVONOIDS, PERMEABILITY, ABSORPTION, MEMBRANES, MODEL
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-7214860
- MLA
- Gonzales, Gerard, et al. “Quercetin Mitigates Valinomycin-Induced Cellular Stress via Stress-Induced Metabolism and Cell Uptake.” MOLECULAR NUTRITION & FOOD RESEARCH, vol. 60, no. 5, 2016, pp. 972–80, doi:10.1002/mnfr.201500999.
- APA
- Gonzales, G., Smagghe, G., Vissenaekens, H., Grootaert, C., Rajkovic, A., Van de Wiele, T., … Van Camp, J. (2016). Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake. MOLECULAR NUTRITION & FOOD RESEARCH, 60(5), 972–980. https://doi.org/10.1002/mnfr.201500999
- Chicago author-date
- Gonzales, Gerard, Guy Smagghe, Hanne Vissenaekens, Charlotte Grootaert, Andreja Rajkovic, Tom Van de Wiele, Katleen Raes, and John Van Camp. 2016. “Quercetin Mitigates Valinomycin-Induced Cellular Stress via Stress-Induced Metabolism and Cell Uptake.” MOLECULAR NUTRITION & FOOD RESEARCH 60 (5): 972–80. https://doi.org/10.1002/mnfr.201500999.
- Chicago author-date (all authors)
- Gonzales, Gerard, Guy Smagghe, Hanne Vissenaekens, Charlotte Grootaert, Andreja Rajkovic, Tom Van de Wiele, Katleen Raes, and John Van Camp. 2016. “Quercetin Mitigates Valinomycin-Induced Cellular Stress via Stress-Induced Metabolism and Cell Uptake.” MOLECULAR NUTRITION & FOOD RESEARCH 60 (5): 972–980. doi:10.1002/mnfr.201500999.
- Vancouver
- 1.Gonzales G, Smagghe G, Vissenaekens H, Grootaert C, Rajkovic A, Van de Wiele T, et al. Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake. MOLECULAR NUTRITION & FOOD RESEARCH. 2016;60(5):972–80.
- IEEE
- [1]G. Gonzales et al., “Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake,” MOLECULAR NUTRITION & FOOD RESEARCH, vol. 60, no. 5, pp. 972–980, 2016.
@article{7214860, abstract = {{Scope: Intestinal cells are constantly exposed to luminal toxins. In this study, we investigated the effect of cellular stress caused by valinomycin, which is structurally and functionally similar to the bacterial toxin cereulide, on quercetin metabolism and cellular localization in undifferentiated cells. Methods and results: Coadministration of quercetin and valinomycin (50 mu M quercetin/0.05 mu M valinomycin) reduced intracellular reactive oxygen species content and increased cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) of Caco-2 cells compared to valinomycin-only (0.05 mu M) treatment. Quercertin was effectively metabolized into methyl, glucuronide, and sulfate conjugates, which were mostly secreted into to the culture medium. Three different O-methylated quercetin isomers were detected. Two were exported from the cells and one remained intracellularly. Further, valinomycin caused an increase in the intracellular accumulation of O-methylated quercetin metabolites compared to cells treated only with quercetin. In valinomycin-untreated cells, quercetin and O-methylated quercetin metabolite were localized in the cell membrane, whereas valinomycin treatment resulted in their uptake by the cells. Conclusion: This is the first report on the change in metabolism, localization, and accumulation of O-methylated quercetin metabolites in undifferentiated Caco-2 cells as a response during stress caused by valinomycin. These results indicate a potential cellular stress response mechanism in undifferentiated Caco-2 cells, which adds novel insights into the mechanisms of flavonoid cellular bioactivity.}}, author = {{Gonzales, Bryan and Smagghe, Guy and Vissenaekens, Hanne and Grootaert, Charlotte and Rajkovic, Andreja and Van de Wiele, Tom and Raes, Katleen and Van Camp, John}}, issn = {{1613-4125}}, journal = {{MOLECULAR NUTRITION & FOOD RESEARCH}}, keywords = {{Metabolism,Caco-2,Methylquercetin,Quercetin,Valinomycin,ANTIOXIDANT ACTIVITY RELATIONSHIPS,CACO-2 CELLS,CAULIFLOWER WASTE,MASS-SPECTROMETRY,IN-VITRO,FLAVONOIDS,PERMEABILITY,ABSORPTION,MEMBRANES,MODEL}}, language = {{eng}}, number = {{5}}, pages = {{972--980}}, title = {{Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake}}, url = {{http://doi.org/10.1002/mnfr.201500999}}, volume = {{60}}, year = {{2016}}, }
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