Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Effects on apoSOD1 Structure and Dynamics
2.2. Effects on apoSOD1 Aggregation Kinetics
2.3. Effects on the Size, Solubility, and Morphology of apoSOD1 Aggregates
3. Experimental Section
3.1. Chemicals and Proteins
3.2. Fluorescence Spectroscopy
3.3. Circular Dichroism (CD)
3.4. Differential Scanning Fluorimetry
3.5. Trypsin Limited Proteolysis
3.6. SOD1 Aggregation Assays
3.7. Dynamic Light Scattering (DLS)
3.8. Nanoparticle Tracking Analysis (NTA)
3.9. Quantification of Insoluble Aggregates
3.10. Transmission Electron Microscopy
4. Conclusions
Acknowledgments
Conflicts of Interest
References
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Compound | Compound properties | CSF levels (μM) | Sporadic ALS | ||
---|---|---|---|---|---|
Type | Physiological charge | Normal | Altered | ||
l-Arginine | +1 | 15–25 | 6–21 | decreased | |
l-Lysine | amino acid | +1 | 18–30 | 45 | decreased |
l-Ornithine | +1 | 4–8 | 7–8 | unchanged | |
Glyceric acid | sugar acid | −1 | 34 | n.a. | decreased |
Phthalate | exogenous | −2 | n.a. | n.a | unchanged |
Fructose | monosaccharide | 0 | 160–240 | n.a. | decreased |
Erythronic Acid | −1 | 5 | n.a | unchanged |
Compound | Lag time tlag, h | Aggregation rate kapp, h−1 |
---|---|---|
Control (no compound) | 88 | 0.040 |
Erythronic Acid | 47 | 0.093 |
l-Ornithine | 20 | 0.062 |
Phthalate | 24 | 0.059 |
l-Arginine | 41 | 0.054 |
Glyceric acid | 39 | 0.044 |
Fructose | 17 | 0.044 |
l-Lysine | n.d. | 0.019 |
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Cristóvão, J.S.; Leal, S.S.; Cardoso, I.; Gomes, C.M. Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation. Int. J. Mol. Sci. 2013, 14, 19128-19145. https://doi.org/10.3390/ijms140919128
Cristóvão JS, Leal SS, Cardoso I, Gomes CM. Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation. International Journal of Molecular Sciences. 2013; 14(9):19128-19145. https://doi.org/10.3390/ijms140919128
Chicago/Turabian StyleCristóvão, Joana S., Sónia S. Leal, Isabel Cardoso, and Cláudio M. Gomes. 2013. "Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation" International Journal of Molecular Sciences 14, no. 9: 19128-19145. https://doi.org/10.3390/ijms140919128