Numerous studies have investigated changes in protein expression at the system level using proteomic mass spectrometry, but only recently have studies explored the structure of proteins at the proteome level. We developed covalent protein painting (CPP), a protein footprinting method that quantitatively labels exposed lysine, and have now extended the method to whole intact animals to measure surface accessibility as a surrogate of in vivo protein conformations. We investigated how protein structure and protein expression change as Alzheimer's disease (AD) progresses by conducting in vivo whole animal labeling of AD mice. This allowed us to analyze broadly protein accessibility in various organs over the course of AD. We observed that structural changes of proteins related to 'energy generation,' 'carbon metabolism,' and 'metal ion homeostasis' preceded expression changes in the brain. We found that proteins in certain pathways undergoing structural changes were significantly co-regulated in the brain, kidney, muscle, and spleen.
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http://dx.doi.org/10.1101/2023.05.29.542496 | DOI Listing |
ACS Nano
January 2025
Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States.
Gut dysbiosis contributes to multiple pathologies, yet the mechanisms of the gut microbiota-mediated influence on systemic and distant responses remain largely elusive. This study aimed to identify the role of nanosized bacterial extracellular vesicles (bEVs) in mediating allodynia, i.e.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Division of Physiological Chemistry and Metabolism, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-0011, Japan.
Macrophages remove apoptotic cells via phagocytosis, also known as efferocytosis, during inflammation to maintain tissue homeostasis. This process is accompanied by various metabolic changes in macrophages including the production of lipid metabolites by fatty acid oxygenases. Among these, highly reactive metabolites, called lipid-derived electrophiles (LDEs), modify cysteines and other nucleophilic amino acids in intracellular proteins.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Molecular Diagnostic Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People's Hospital, Hangzhou 310006, China.
The designability and high reactivity of nanotechnology provide strategies for antitumor therapy by regulating the redox state in tumor cells. Here, we synthesize a kind of vanadium dioxide nanoparticle encapsulated in bovine serum albumin and containing disulfide bonds (VSB NPs) for photothermal-enhanced ferroptosis and pyroptosis effects. Mechanism studies show that disulfide bonds can effectively consume overexpressed glutathione (GSH) in the tumor microenvironment, leading to a decrease in glutathione peroxidase 4 (GPX4) activity.
View Article and Find Full Text PDFEgypt J Immunol
January 2025
Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
The autoimmune disease systemic lupus erythematosus (SLE) is presented with many clinical symptoms. The transcription factor fork head box protein 3 (Foxp3) is expressed on regulatory T (T-reg) cells and essential for its development and function. Functional single-nucleotide polymorphisms (SNPs) in the Foxp3-3279 (rs3761548 C/A) gene influence SLE pathogenesis.
View Article and Find Full Text PDFEgypt J Immunol
January 2025
Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
Multiple sclerosis (MS) is a disease of the central nervous system, characterized by progressive demyelination and inflammation. MS is characterized by immune system attacks on the myelin sheath surrounding nerve fibers. Genome-wide association studies revealed a polymorphism in the signal transducer and activator of transcription 4 (STAT4) gene that increases risk for MS.
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