Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer’s Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways
Abstract
:1. Introduction
- Examine the early aging-, sex-, and disease-dependent changes in MSox levels;
- Identify peptide and protein targets specifically sensitive and resistant to the oxidation of methionine;
- Validate key changes with peptide-based absolute quantification; and
- Explore the stability of key MSox sites to handling and storage.
2. Results
2.1. Experimental Design
2.2. Age-Dependent Increase in Global MSox
2.3. Pathway Analysis Reveals Distinct Age-Dependent Signatures
2.4. High-Abundance Proteins Are Susceptible to MSox Accumulation
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Label-Free Quantitative Proteomic Analysis
5.2. PRM
5.2.1. Sample Preparation for PRM Assay
5.2.2. Development and Analytical Validation of Targeted MS Assays/Measurements
5.3. Enrichment Pathway Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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(A) | 3 Months | 6 Months | 9 Months | |||
WT | 5XFAD | WT | 5XFAD | WT | 5XFAD | |
MSox peptides | 396 | 396 | 603 | 606 | 819 | 822 |
MSox proteins | 228 | 228 | 282 | 285 | 358 | 358 |
MSox % | 3.59 | 3.59 | 4.20 | 4.22 | 4.48 | 4.48 |
(B) | 3 Months | 5XFAD Mice 6 Months | 9 Months | |||
Female | Male | Female | Male | Female | Male | |
MSox peptides | 396 | 395 | 597 | 602 | 821 | 820 |
MSox proteins | 228 | 228 | 283 | 284 | 358 | 357 |
MSox % | 3.59 | 3.58 | 4.16 | 4.19 | 4.48 | 4.47 |
MSox | Proteome | ||||||
---|---|---|---|---|---|---|---|
Enriched Terms | 3 M | 6 M | 9 M | 3 M | 6 M | 9 M | |
Reactome Pathways | Glucose metabolism | 1.76 × 10−2 | 7.05 × 10−5 | 5.92 × 10−5 | 1.00 × 100 | 1.00 × 100 | 5.56 × 10−1 |
Immune system | 1.05 × 10−2 | 3.90 × 10−3 | 9.34 × 10−5 | 4.28 × 10−1 | 1.76 × 10−5 | 1.31 × 10−11 | |
Gluconeogenesis | 1.31 × 10−2 | 3.32 × 10−4 | 1.22 × 10−4 | 6.58 × 10−1 | 1.00 × 100 | 1.00 × 100 | |
Organelle biogen and maintenance | 1.17 × 10−2 | 4.46 × 10−3 | 4.07 × 10−4 | 1.00 × 100 | 2.99 × 10−1 | 7.69 × 10−2 | |
Transport of small molecules | ns | 6.46 × 10−4 | 4.29 × 10−4 | 4.53 × 10−1 | 7.23 × 10−1 | 1.33 × 10−1 | |
Transmission chemical synapses | 9.80 × 10−3 | 5.43 × 10−4 | 6.07 × 10−4 | 1.00 × 100 | 7.11 × 10−1 | 2.47 × 10−2 | |
Innate immune system | ns | 1.49 × 10−2 | 8.32 × 10−4 | 4.47 × 10−1 | 9.58 × 10−6 | 1.25 × 10−11 | |
Signal transduction | 3.65 × 10−2 | 2.43 × 10−2 | 8.37 × 10−4 | 3.64 × 10−1 | 4.04 × 10−1 | 2.89 × 10−4 | |
L1CAM interactions | 6.47 × 10−3 | 6.29 × 10−4 | 5.59 × 10−3 | 4.64 × 10−2 | 1.70 × 10−1 | 1.14 × 10−4 | |
Recycling pathway of L1 | 1.05 × 10−2 | 6.32 × 10−4 | 1.27 × 10−3 | 2.44 × 10−1 | 4.15 × 10−1 | 1.15 × 10−3 | |
Glycolysis | 1.18 × 10−2 | 7.92 × 10−4 | 2.44 × 10−3 | 1.00 × 100 | 1.00 × 100 | 8.12 × 10−1 | |
Neurotransmitter release cycle | 1.03 × 10−2 | 8.38 × 10−4 | 2.66 × 10−3 | 1.00 × 100 | ns | 9.68 × 10−2 | |
Cellular Component | Cytoplasm | ns | ns | ns | 1.41 × 10−215 | 1.49 × 10−243 | 9.63 × 10−263 |
Intracellular anatomical structure | ns | ns | ns | 3.51 × 10−152 | 1.19 × 10−166 | 6.39 × 10−186 | |
Cytosol | ns | ns | ns | 8.87 × 10−98 | 4.40 × 10−103 | 4.91 × 10−107 | |
Organelle | 7.42 × 10−3 | ns | 5.02 × 10−3 | 3.12 × 10−113 | 3.30 × 10−124 | 9.44 × 10−128 | |
Postsynapse | 3.53 × 10−2 | 5.53 × 10−3 | 6.98 × 10−3 | 2.48 × 10−112 | 5.86 × 10−117 | 4.81 × 10−112 | |
Axon | 3.05 × 10−9 | 2.80 × 10−7 | 4.35 × 10−6 | 5.43 × 10−58 | 2.93 × 10−64 | 2.52 × 10−62 | |
Myelin sheath | 2.94 × 10−29 | 1.76 × 10−30 | 5.49 × 10−30 | 7.26 × 10−79 | 2.27 × 10−72 | 1.72 × 10−68 |
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Lopes, F.B.T.P.; Schlatzer, D.; Li, M.; Yilmaz, S.; Wang, R.; Qi, X.; Ayati, M.; Koyutürk, M.; Chance, M.R. Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer’s Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways. Int. J. Mol. Sci. 2024, 25, 6516. https://doi.org/10.3390/ijms25126516
Lopes FBTP, Schlatzer D, Li M, Yilmaz S, Wang R, Qi X, Ayati M, Koyutürk M, Chance MR. Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer’s Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways. International Journal of Molecular Sciences. 2024; 25(12):6516. https://doi.org/10.3390/ijms25126516
Chicago/Turabian StyleLopes, Filipa Blasco Tavares Pereira, Daniela Schlatzer, Mengzhen Li, Serhan Yilmaz, Rihua Wang, Xin Qi, Marzieh Ayati, Mehmet Koyutürk, and Mark R. Chance. 2024. "Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer’s Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways" International Journal of Molecular Sciences 25, no. 12: 6516. https://doi.org/10.3390/ijms25126516