Document Type
Article
Publication Date
6-13-2024
Abstract
Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from reactive oxygen species (ROS), whose chemistries are linked to various disease pathologies, including neurodegeneration. Emerging evidence shows MSox site occupancy is, in some cases, under enzymatic regulatory control, mediating cellular signaling, including phosphorylation and/or calcium signaling, and raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age-, sex-, and disease-dependent MSox speciation in the mouse hippocampus. In addition, we explored the chemical stability and statistical variance of oxidized peptide signals to understand the needed power for MSox-based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of the mouse hippocampus. Further, this paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for novel target identification in biological discovery and for biomarker analysis in ROS and other oxidation-linked diseases.
Recommended Citation
Lopes, Filipa Blasco Tavares Pereira, Daniela Schlatzer, Mengzhen Li, Serhan Yilmaz, Rihua Wang, Xin Qi, Marzieh Ayati, Mehmet Koyutürk, and Mark R. Chance. "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 (2024): 6516. https://doi.org/10.3390/ijms25126516
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
International Journal of Molecular Sciences
DOI
https://doi.org/10.3390/ijms25126516
Comments
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).