PXD049417-1
PXD049417 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Multiomics approach to decipher pathophysiological mechanisms and therapeutic impact of methionine restriction in cystathionine β-synthase deficient homocystinuria |
Description | Background. Cystathionine β-synthase (CBS)-deficient homocystinuria (HCU) is an inherited disorder of sulfur amino acid metabolism with varying severity and organ complications, and a limited knowledge about underlying pathophysiological processes. Here we aimed at getting an in-depth insight into disease mechanisms using a transgenic mouse model of HCU (I278T). Methods. We assessed metabolic, proteomic and sphingolipidomic changes, and mitochondrial function in tissues and body fluids of I278T mice and WT controls. Furthermore, we evaluated the efficacy of methionine-restricted diet (MRD) in I278T mice. Results. In WT mice, we observed a distinct tissue/body fluid compartmentalization of metabolites with up to six-orders of magnitude differences in concentrations among various organs. The I278T mice exhibited the anticipated metabolic disbalance with signs of an increased production of hydrogen sulfide and disturbed persulfidation of free aminothiols. HCU resulted in a significant dysregulation of liver proteome affecting biological oxidations, conjugation of compounds, and metabolism of amino acids, vitamins, cofactors and lipids. Liver phospholipidomics indicated upregulation of the pro-proliferative sphingomyelin-ceramide-sphingosine-1-phosphate signaling pathway. Liver mitochondrial function of HCU mice did not seem to be impaired compared to controls. MRD in I278T mice improved metabolic balance in all tissues and substantially reduced dysregulation of liver proteome. Conclusion. The study highlights distinct tissue compartmentalization of sulfur-related metabolites in normal mice, extensive metabolic, proteomic and sphingolipidomic disruptions in I278T mice, and the efficacy of MRD to alleviate some of the HCU-related biochemical abnormalities. |
HostingRepository | PRIDE |
AnnounceDate | 2024-07-03 |
AnnouncementXML | Submission_2024-07-03_02:18:36.544.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD049417 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Ondrej Vit |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-02-16 00:27:37 | ID requested | |
⏵ 1 | 2024-07-03 02:18:37 | announced |
Publication List
10.1016/j.redox.2024.103222; |
10.6019/PXD049417; |
Majtan T, Olsen T, Sokolova J, Krijt J, K, ř, í, ž, kov, á M, Ida T, Ditr, ó, i T, Hansikova H, Vit O, Petrak J, Kucha, ř L, Kruger WD, Nagy P, Akaike T, Ko, ž, ich V, Deciphering pathophysiological mechanisms underlying cystathionine beta-synthase-deficient homocystinuria using targeted metabolomics, liver proteomics, sphingolipidomics and analysis of mitochondrial function. Redox Biol, 73():103222(2024) [pubmed] |
Keyword List
submitter keyword: Cystathionine beta-synthase |
homocystinuria |
methionine restriction |
metabolomics |
proteomics |
Contact List
Jiri Petrak | |
---|---|
contact affiliation | BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic |
contact email | jpetr@lf1.cuni.cz |
lab head | |
Ondrej Vit | |
contact affiliation | Charles University, First Faculty of Medicine, BIOCEV |
contact email | ondrvit@gmail.com |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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