PXD031782

PXD031782 is an original dataset announced via ProteomeXchange.

Title	Label-free quantitative (LFQ) proteomic analysis of redox mediated posttranslational modifications (PTM) in the cartilage from young and old osteoarthritis (OA) mice with or without the senolytic treatment
Description	Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response. However, recent research studies showed that the therapeutic benefit is reduced in aged mice. Increased oxidative stress (redox) mediates metabolic dysregulation and accumulation of posttranslational modifications (PTM) on proteins from the cartilage and is one of the major hallmarks of advanced age. This research investigated whether the senolytic treatment differentially affects oxidative load in the joints from young and aged animals. We employed label-free quantitative (LFQ) analysis of changes in the protein expression profiles and associated carbonylated PTMs in the extracted joint proteins. Our proteomic survey focused to a set of PTMs described as advanced glycation-end products (AGEs) or advanced lipooxidation-end products (ALEs), known to accumulate during aging and age-associated diseases. AGEs and ALEs are the result of non-enzymatic reactions of protein with reducing sugars, or with oxidized sugar or lipid degradation products, which may alter and sometimes crosslink the positively charged amino acids lysine and arginine on proteins. Our proteomic dataset supported detection of several AGEs and ALEs, including the adducts 4-ONE (4-oxononenal), 4-ONE+Delta:H(-2)O(-1) (dehydrated 4-oxononenal Michael adduct), carboxyethyl, carboxymethyl, 3-deoxyglucosone derived dihydroxyimidazoline, G-H1 (glyoxal-derived hydroimidazolone), HNE (4-hydroxynonenal), several carbonylated adducts including proline to pyrrolidinone or pyrrolidone Other detected modifications of note include mono-oxidation and di-oxidation products, including tryptophan to kynurenine. We also detected lysine-epsilon-gly-gly (GlyGly), which marks ubiquitylated sites, indicating potential substrates of proteasome-dependent degradation. The grand total PTM change was negative for treated aged OA mice but positive for treated young OA mice, regardless of whether summed across modifications or across proteins. In other words, senolytic treatment reduced oxidation associated PTMs more effectively in aged OA mice than in young OA mice. The LFQ proteomics analysis was complemented with new biophysical computational tools aimed to predict the stability of carbonylated proteins extracted from the joints. The biophysical model predicted divergent proteomic responses between young and aged animals. Altogether, our results showed that senolysis reduces overall oxidative stress in the aged arthritic joints in vivo.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:03:55.869.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031782
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cristina Clement
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	L-methionine sulfone; N'-formyl-L-kynurenine; L-allysine; L-2-aminoadipic acid; acetylated residue; monohydroxylated residue; L-cysteic acid (L-cysteine sulfonic acid); glutamyl semialdehyde (Arg); iodoacetic acid derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-21 03:08:14	ID requested
1	2023-09-26 10:28:27	announced
⏵ 2	2024-10-22 06:03:56	announced	2024-10-22: Updated project metadata.

10.6019/PXD031782;

submitter keyword: mouse model of osteoarthritis (OA)

senolytic treatment

label-free quantitative (LFQ) proteomic

analysis of redox PTMs in the cartilage proteins

Jennifer H. Elisseeff PhD
contact affiliation	Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
contact email	jhe@jhu.edu
lab head
Cristina Clement
contact affiliation	Weill Cornell Medicine
contact email	ccc4002@med.cornell.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031782
     1. Label: PRIDE project
     2. Name: Label-free quantitative (LFQ) proteomic analysis of redox mediated posttranslational modifications (PTM) in the cartilage from young and old osteoarthritis (OA) mice with or without the senolytic treatment