Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae
Abstract
:1. Introduction
2. Result and Discussion
2.1. Thiol Reduction of MSeA, MeSeSG, and DMDSe
2.2. Enzymatic Reduction by Glutathione Reductase and Thioredoxin Reductase
2.3. Toxicity of MeSeH Precursors
2.4. Selenium Content of Cells Exposed to MeSeH Precursors
2.5. Exposure to MeSeH Causes Protein Aggregation
3. Conclusions
4. Materials and Methods
4.1. Reagents and Enzymes
4.2. Spectrophotometric Measurements
4.3. MeSeSG Purification
4.4. Stopped-Flow Experiments
4.5. Determination of DMDSe Redox Potential
4.6. Data Analysis
4.7. Enzymatic Assays
4.8. Strains and Media
4.9. Toxicity Assays
4.10. Determination of Selenium Content
4.11. Fluorescence Microscopy
4.12. Fluorescence Spectroscopy
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Initial Concentrations (µM) | K2 | k−1 (M−1.s−1) | k1 (M−1.s−1) | ||
---|---|---|---|---|---|
DMDSe | GSH | GSSG | |||
100 | 1000 | 15 * | 1288 ± 7 | 431 ± 8 | 0.45 ± 0.02 |
100 | 1000 | 15 * + 50 | 1184 ± 10 | 311 ± 4 | 0.46 ± 0.02 |
100 | 2500 | 37.5 * | 812 ± 4 | 232 ± 3 | 0.54 ± 0.01 |
100 | 5000 | 75 * | 1222 ± 5 | 226 ± 2 | 0.15 ± 0.01 |
200 | 2500 | 37.5 * | 902 ± 5 | 388 ± 4 | 0.30 ± 0.01 |
200 | 5000 | 75 * | 994 ± 10 | 362 ± 5 | 0.27 ± 0.01 |
MeSeH (µM) | GSSG (µM) | Rate Constant k−1 (M−1.s−1) | GSH (µM) | DMDSe (µM) | Rate Constant k−2 (M−1.s−1) |
---|---|---|---|---|---|
25 | 100 | 418 ± 32 | 1250 | 50 | 2.9 ± 0.7 104 |
50 | 200 | 434 ± 43 | 1667 | 67 | 4.3 ± 1.3 104 |
50 | 300 | 365 ± 70 | 2500 | 100 | 3.6 ± 0.9 104 |
50 | 400 | 351 ± 140 | 1250 | 125 | 3.9 ± 1.3 104 |
100 | 400 | 356 ± 35 | |||
100 | 600 | 322± 54 |
Strain | Se Compound Added | Concentration | Total Se (µg/g Dry Weight) |
---|---|---|---|
BY4742 | MSeA | 30 µM | 162 ± 32 |
MSeA | 300 µM | 314 ± 25 | |
MSeA | 10 mM | 4053 ± 455 | |
MSeA /GSH mix | 30 µM + 90 µM | 2331 ± 600 | |
DMDSe | 5 µM | 1378 ± 290 |
BY4742 | BY4742-∆met17 | ||||
---|---|---|---|---|---|
Se Compound Added | Concentration | Total Se in Water Fraction | SeMet | Total Se in Water Fraction | SeMet |
MSeA | 300 µM | 118 ± 16 | 47 ± 11 | 67 ± 17 | 12 ± 5 |
MSeA/GSH mix | 30 µM + 90 µM | 1462 ± 515 | 349 ± 159 | 33 ± 6 | 6 ± 0.5 |
DMDSe | 5 µM | 573 ± 49 | 81 ± 41 | 21 ± 5 | 7.5 ± 3 |
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Dauplais, M.; Bierla, K.; Maizeray, C.; Lestini, R.; Lobinski, R.; Plateau, P.; Szpunar, J.; Lazard, M. Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae. Int. J. Mol. Sci. 2021, 22, 2241. https://doi.org/10.3390/ijms22052241
Dauplais M, Bierla K, Maizeray C, Lestini R, Lobinski R, Plateau P, Szpunar J, Lazard M. Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae. International Journal of Molecular Sciences. 2021; 22(5):2241. https://doi.org/10.3390/ijms22052241
Chicago/Turabian StyleDauplais, Marc, Katarzyna Bierla, Coralie Maizeray, Roxane Lestini, Ryszard Lobinski, Pierre Plateau, Joanna Szpunar, and Myriam Lazard. 2021. "Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae" International Journal of Molecular Sciences 22, no. 5: 2241. https://doi.org/10.3390/ijms22052241