PXD052143

PXD052143 is an original dataset announced via ProteomeXchange.

Title	Cardio-metabolic and cytoskeletal proteomic signatures differentiate stress hypersensitivity in dystrophin-deficient mdx mice
Description	Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female mdx mice were phenotypically stratified into “stress-resistant” or “stress-sensitive” groups based on their response to two laboratory stressors. Quantitative proteomics of striated muscle (heart and tibialis anterior) revealed clustering of the proteome according to sex and stress hypersensitivity. In both muscles, stress-resistant females were most dissimilar from all other groups, with over 250 proteins differentially regulated between stress-resistant and stress-sensitive females in each muscle. Males showed less proteomic variation with stress sensitivity, however these changes were associated with clear pathway enrichment. In the heart, stress-sensitive males had significant enrichment of pathways related to mitochondrial ATP synthesis, suggesting that increased cardio-metabolic capacity is associated with stress hypersensitivity in male mdx mice. Independent of striated muscle source or sex, stress hypersensitivity was associated with altered expression of beta-actin-like protein 2 (ACTBL2), an actin isoform critical for the formation of focal adhesions and cell motility. Stress-sensitive individuals had higher expression of ACTBL2, indicative of altered cytoskeletal organisation. Despite identifying proteomic signatures associated with stress hypersensitivity, these did not correlate with differences in the serum metabolome acutely after a stressor. These data suggest that the heterogeneity in stress hypersensitivity in mdx mice is partially driven by cytoskeletal organisation, but that sex-specific cardio-metabolic reprogramming may also play a role in this phenotype
HostingRepository	PRIDE
AnnounceDate	2024-12-29
AnnouncementXML	Submission_2024-12-28_17:00:54.499.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD052143
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monoacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-09 07:38:15	ID requested
⏵ 1	2024-12-28 17:00:54	announced

10.6019/PXD052143;

10.1016/J.JPROT.2024.105371;

submitter keyword: fear, proteomics,Duchenne muscular dystrophy, stress, cytoskeletal organisation, mitochondrial function

Albert Lee
contact affiliation	Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, NSW, 2109 Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/12/PXD052143

PRIDE project URI

• PRIDE
  1. PXD052143
     1. Label: PRIDE project
     2. Name: Cardio-metabolic and cytoskeletal proteomic signatures differentiate stress hypersensitivity in dystrophin-deficient mdx mice