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PXD025321

PXD025321 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIntegrated molecular landscape perturbations underlie cellular responses during hyperammonemia
DescriptionAmmonia is a cytotoxic molecule generated during cellular functions and by the gut microbiome. Dysregulated ammonia metabolism initiates a hyperammonemic stress response (HASR). Hyperammonemia occurs in many chronic diseases but there is limited understanding of the overall consequences of HASR. A comprehensive array of unbiased approaches was used to identify global responses during hyperammonemia with experimental validation of critical findings. Protein/gene expression and chromatin accessibility in hyperammonemic murine myotubes and mouse skeletal muscle tissue were analyzed by quantitative proteomics, RNA sequencing (RNAseq), and Assay for Transposase Accessible Chromatin Sequencing (ATACseq). Unique clusters of expression/accessibility changes were identified in hyperammonemic myotubes. In hyperammonemic mouse muscle and myotubes, we identified enrichment of pathways involved in oxidative phosphorylation, calcium signaling, hypoxia inducible factor-1, and apoptosis and regulation of protein synthesis were altered during HASR and were experimentally validated. Enrichment of senescence signaling and glycosylation pathways during HASR were novel observations. Comparisons with RNAseq data from skeletal muscle from human patients with cirrhosis revealed similar perturbations, demonstrating the translational relevance of our observations. We identified several novel regulatory pathways during HASR that are conserved in different models and across species, and whose dysregulation could significantly impact skeletal muscle structure and function.
HostingRepositoryPRIDE
AnnounceDate2021-07-27
AnnouncementXMLSubmission_2021-07-27_07:00:26.647.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLing Li
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-12 11:07:04ID requested
12021-07-27 07:00:27announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: C2C12 myotubes, skeletal muscle, hyperammonemia
Contact List
Srinivasan Dasarathy
contact affiliationDepartment of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic
contact emailDASARAS@ccf.org
lab head
Ling Li
contact affiliationCleveland Clinic
contact emaillil5@ccf.org
dataset submitter
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