{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Tabular":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/diann-output.tsv","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/File_name_to_sample.tsv"],"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380004.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380002.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380013.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380006.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380010.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380009.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380015.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380005.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380007.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380016.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380001.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380012.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380011.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380014.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380008.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD079332/25NP11380003.raw"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["yuxi.feng@medma.uni-heidelberg.de"],"submitter":["Yuxi Feng"],"technology_type":["Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"software":["Not available"],"submitter_keywords":["Prediabetes; diabetes; ndpk-b; hbp; diabetic cardiomyopathy; mitochondria","mitochondria","hbp","diabetic cardiomyopathy","ndpk-b","Prediabetes","diabetes"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD079332"],"tissue":["Heart"],"sample_protocol":["LV tissue from non-diabetic and diabetic WT and NDPK-B-deficient mice was processed for enrichment of O-GlcNAc-modified proteins followed by mass spectrometry-based analysis. Cardiac tissue was homogenized in 240 µl ice-cold RIPA lysis buffer, and protein concentrations were determined using a BCA assay. For each sample, 0.5 mg of total protein was incubated with 30 µl of succinylated wheat germ agglutinin (sWGA) agarose beads to selectively capture O-GlcNAc-modified proteins. The samples were rotated gently for 24 h at 4 °C to allow binding. Subsequently, the beads were washed repeatedly to remove unbound proteins, and the enriched O-GlcNAc-containing protein fraction was recovered and subjected to LC-MS/MS analysis. Proteins were eluted in 100 µl urea-HEPES lysis buffer, heated at 56 °C for 20 min, cooled, and centrifuged at 25,000 g for 15 min at 4 °C.  Proteins were reduced with 10 mM Dithiothreitol (30 min, 37 °C), alkylated with 55 mM iodoacetamide (45 min, dark), and digested with sequencing-grade trypsin. Peptides were desalted and analyzed by nanoLC-MS/MS in Data-Independent Acquisition mode on an Astral mass spectrometer coupled to a Vanquish Neo nanoLC system (Thermo Fisher Scientific, USA) according to the manufacturer’s recommendations."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["The sample data were further processed by bioinformatic analysis with the Program R (Version 4.4.3). Proteins with less than three quantified data points were omitted from subsequent analyses. Principal Component Analysis (PCA) was performed on log2-transformed, normalized label-free intensities from the O-GlcNAc immunoenriched cardiac proteomes of four groups. Volcano plots were generated for the indicated pairwise contrasts: WTDC to WT NC, NDPK-B-/-NC to WTNC, NDPK-B-/-DC to WTDC, and NDPK-B-/-DC to NDPK-B-/-NC. Fold changes were calculated as the ratio of group means (log2 scale), and proteins were considered differentially enriched at nominal p < 0.05 and absolute fold change ≥ 1.2 (|log2FC| ≥ 0.2630). Proteins above threshold were classified as increased or decreased. Pathway annotation was created with Metascape, used a two-contrast intersection strategy. Proteins increased in WTDC relative to WTNC and in those increased in NDPK-B-/-NC relative to WTNC were subjected to Gene Ontology (GO) over-representation analysis (biological process, BP, cellular component, CC, molecular function, MF). GO terms significant in both were intersected to define WT-diabetic-elevated pathways. Top terms are shown as bar plots. Proteins belonging to consensus pathways were Z-scored by row and visualized as hierarchically clustered heat maps."],"omics_type":["Proteomics"],"labhead":["Yuxi Feng"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Experimental Pharmacology Mannheim (EPM), European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"],"species":["Mus Musculus (mouse)"],"publication":["Not available"],"submitter_mail":["yuxi.feng@medma.uni-heidelberg.de"],"submitter_affiliation":["Experimental Pharmacology Mannheim (EPM), European Center of Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"],"submitter_country":["Germany"],"additional_accession":[]},"is_claimable":false,"name":"Early cardiomyopathy in prediabetic NDPK-B-deficient mice is linked to dysregulated O-GlcNAcylation of mitochondrial proteins","description":"Diabetic cardiomyopathy (DCM) is initiated independently of other cardiac risk factors and is characterized by an early, often clinically silent decline in myocardial function. Nucleoside-diphosphate-kinase B (NDPK-B) plays a critical role in ion channel regulation and signal transduction, and its genetic deletion in middle-aged mice induces a phenotype resembling diabetic cardiomyopathy. The present study investigated the contribution of protein O-GlcNAcylation, driven by the hexosamine biosynthesis pathway (HBP), to the initiation and progression of DCM. NDPK-B-deficient prediabetic mice and streptozotocin-induced diabetic mice were examined. In both models, left ventricles (LV) exhibited increased extracellular matrix deposition and a marked diastolic dysfunction. Concomitantly, activation of the HBP was observed in prediabetic and diabetic LVs. Proteomic profiling of O-GlcNAcylated proteins revealed substantial dysregulation of mitochondrial proteins under prediabetic conditions, particularly affecting components of respiratory complex I, along with metabolic fuel reprogramming and activation of immune and inflammatory pathways. Progression to overt DCM was associated with a shift toward lipid-driven metabolic remodeling and profound structural mitochondrial impairment. These findings identify aberrant mitochondrial O-GlcNAcylation as a key early event in the initial stages of cardiac damage and reveal a mechanism involved in prediabetic cardiomyopathy.","dates":{"publication":"2026-06-08","submission":"2026-06-06"},"accession":"PXD079332","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:1584","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:7719","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:2853422","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:1640278","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:906914","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:33941","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:42410","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:9995","NEWT:575412","NEWT:28112","NEWT:49012","NEWT:6493","NEWT:10832","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:1613","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:353153","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:74426","NEWT:443906","NEWT:13037","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEW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