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Research article
Global profiles of a cetylated proteins in the brains of scrapie agents 139A- and ME7-infected mice collected at mid-early, mid-late and terminal stage
Xiaoping Dong
China CDC
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background
Acetylation is a reversible post-translational modification in eukaryotic and prokaryotic cells, actively participating in the regulation for biological functions and in the pathogenesis of diseases.
Methods
The acetylated proteins from the cortex regions of scrapie agents 139A- and ME7-infected mice collected at mid-early (80 days post-infection, dpi), mid-late (120 dpi) and terminal stage (180 dpi) were extracted. The global profiles of the brain acetylated proteins were assayed with proteomic mass spectrometry. The acetylated peptides whose levels were >1.5-fold higher or lower than that of age-matched normal controls were considered as differentially expressed acetylated peptides (DEAPs).
Results
A total of 1,485 acetylated peptides were identified. 118, 42 and 51 DEAPs were in the brains of 139A-80 dpi, 120 dpi and 180 dpi, while 390, 227 and 75 DEAPs were in those of ME7-80 dpi, 120 dpi and 180 dpi, respectively. Overwhelming majority of the DEAPs in mid-early stage was down-regulated, while more portions of DEAPs in mid-late and late stage were up-regulated. Approximately 22.1% (328/1485) acetylated peptides were mitochondrial associated, which were mapped to 74 different proteins. Among them, 44 (59.5%) proteins showed differentially expressed at least at one tested time-point. KEEG pathways analysis identified 39, 13, 10 and 55, 25, 18 pathways in the samples of 80, 120 and 180 dpi of 139A- and ME7-infected mice as significantly changed (P<0.05), respectively. Six pathways were commonly involved in all tested samples, including carbon metabolism, metabolic pathways, biosynthesis of amino acids, glycolysis/gluconeogenesis, pyruvate metabolism and citrate cycle (TCA cycle). Moreover, dozens of steps in TAC cycle were affected via down-regulated acetylation for the relevant enzymes in the mid-early stage, while many steps were affected in the mid-late stage via up-regulated acetylation. In the late stage, the affected steps focused on up-regulated acetylation for succinate dehydrogenase, fumarate hydratase and malate dehydrogenase.
Conclusion
Collectively, Our data here illustrated a picture of global acetylation for brain proteins during prion infection, showing remarkably inhibiting acetylation in the early stage and relatively enhanced acetylation in the late stage.
Keywords
Prion, Scrapie infected mouse, Acetylation, Proteomics, KEEG pathway
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This is a list of supplementary files associated with this preprint. Click to download.
- Table.pdf
- supplementarymaterials.doc
Quality control and determination of the prepared samples for proteomic assays. A. Analysis the proteins each sample with 12% SDS-PAGE with coomassie blue staining. B. The distribution of the digested peptides in the length of amino acid after searched in the Swiss-Prot database. The peptides length in amino acid is showed in X-axis and the frequency of the peptides is showed in Y-axis.
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This is a preprint. It has not completed peer review.
Research article
Global profiles of a cetylated proteins in the brains of scrapie agents 139A- and ME7-infected mice collected at mid-early, mid-late and terminal stage
Xiaoping Dong
China CDC
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Acetylation is a reversible post-translational modification in eukaryotic and prokaryotic cells, actively participating in the regulation for biological functions and in the pathogenesis of diseases.
Methods
The acetylated proteins from the cortex regions of scrapie agents 139A- and ME7-infected mice collected at mid-early (80 days post-infection, dpi), mid-late (120 dpi) and terminal stage (180 dpi) were extracted. The global profiles of the brain acetylated proteins were assayed with proteomic mass spectrometry. The acetylated peptides whose levels were >1.5-fold higher or lower than that of age-matched normal controls were considered as differentially expressed acetylated peptides (DEAPs).
Results
A total of 1,485 acetylated peptides were identified. 118, 42 and 51 DEAPs were in the brains of 139A-80 dpi, 120 dpi and 180 dpi, while 390, 227 and 75 DEAPs were in those of ME7-80 dpi, 120 dpi and 180 dpi, respectively. Overwhelming majority of the DEAPs in mid-early stage was down-regulated, while more portions of DEAPs in mid-late and late stage were up-regulated. Approximately 22.1% (328/1485) acetylated peptides were mitochondrial associated, which were mapped to 74 different proteins. Among them, 44 (59.5%) proteins showed differentially expressed at least at one tested time-point. KEEG pathways analysis identified 39, 13, 10 and 55, 25, 18 pathways in the samples of 80, 120 and 180 dpi of 139A- and ME7-infected mice as significantly changed (P<0.05), respectively. Six pathways were commonly involved in all tested samples, including carbon metabolism, metabolic pathways, biosynthesis of amino acids, glycolysis/gluconeogenesis, pyruvate metabolism and citrate cycle (TCA cycle). Moreover, dozens of steps in TAC cycle were affected via down-regulated acetylation for the relevant enzymes in the mid-early stage, while many steps were affected in the mid-late stage via up-regulated acetylation. In the late stage, the affected steps focused on up-regulated acetylation for succinate dehydrogenase, fumarate hydratase and malate dehydrogenase.
Conclusion
Collectively, Our data here illustrated a picture of global acetylation for brain proteins during prion infection, showing remarkably inhibiting acetylation in the early stage and relatively enhanced acetylation in the late stage.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5