PXD025321

PXD025321 is an original dataset announced via ProteomeXchange.

Title	Integrated molecular landscape perturbations underlie cellular responses during hyperammonemia
Description	Ammonia 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.
HostingRepository	PRIDE
AnnounceDate	2021-07-27
AnnouncementXML	Submission_2021-07-27_07:00:26.647.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 11:07:04	ID requested
⏵ 1	2021-07-27 07:00:27	announced

Dataset with its publication pending

submitter keyword: C2C12 myotubes, skeletal muscle, hyperammonemia

Srinivasan Dasarathy
contact affiliation	Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic
contact email	DASARAS@ccf.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025321
     1. Label: PRIDE project
     2. Name: Integrated molecular landscape perturbations underlie cellular responses during hyperammonemia