Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fractionated proteomics identifies a protein network mitigating resistance exercise-induced damage in human skeletal muscle

ABSTRACT: Resistance exercise (RE) improves strength and muscle mass, with multiple benefits for human health. However, intense RE also induces acute myofibrillar damage. The molecular mechanisms that preserve, mark, degrade and restore damaged proteins in order to to keep skeletal muscle working under RE are incompletely understood. Here we study acute molecular and structural responses to RE-induced damage in repeatedly sampled human skeletal muscle in the unadapted, adapted and deadapted state. We show that acute, repeated and interrupted RE induces dynamic changes of the protein landscape associated with the muscular cytoskeleton and myofibrillar lesions. These changes correlate with changes in phosphorylation that are part of a larger molecular signaling footprint indicative of adaptation and deadaptation. We further identify a functional protein network linked to the muscle maintenance protein BAG3, which comprises the mechanosensory proteins PDLIM3 and XIRP1, the small heat shock proteins HSPB1 and HSPB5 and the lipid droplet associated protein PLIN5. All network components exhibit altered phosphorylation and increased cytoskeletal association after damaging RE and cooperate in the recognition of strained muscular structures and the degradation of damaged proteins through chaperone-assisted selective autophagy (CASA). Our study thus reveals previously unrecognized key regulators of muscle homeostasis in humans.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Myoblast, Cell Culture

SUBMITTER: Sara Bonini

LAB HEAD: Dominic Winter

PROVIDER: PXD074000 | Pride | 2026-05-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SB_4_59_YG_SS_27_R1.raw	Raw
	SB_4_59_YG_SS_27_R2.raw	Raw
	SB_4_59_YG_SS_27_R3.raw	Raw
	SB_4_59_YG_SS_27_R5.raw	Raw
	SB_4_59_YG_SS_27_R6.raw	Raw

Items per page:

1 - 5 of 8

Similar Datasets

HT-SELEX of recombinant C2H2 zinc finger domains of Sall4

Project description:To define the sequence preference of SALL4 C2H2 zinc finger domains, we performed SELEX coupled with high-throughput sequencing (HT-SELEX) using the purified SALL4 ZFC1, ZFC2 and ZFC4 domains combined with no protein control experiment. We re-sequenced the libraries from E-MTAB-9236 with very high coverage to estimate the minimum number of reads required per sample for accurate results.

2022-03-01 | E-MTAB-11484 | biostudies-arrayexpress

Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation

Project description:Elg1, the major subunit of a Replication Factor C-like complex, is critical to ensure genomic stability during DNA replication, and is implicated in controlling chromatin structure. We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication. Measurement of Okazaki fragment length and the micrococcal nuclease sensitivity of newly replicated DNA revealed a defect in nucleosome re-assembly in the absence of Elg1. Using a proteomic approach to identify Elg1 binding partners, we discovered that Elg1 interacts with Rtt106, a histone chaperone implicated in replication-coupled nucleosome assembly that also regulates transcription. We find that Rtt106 recruitment to a number of promoters depends on Elg1. A central role for Elg1 is the unloading of PCNA from chromatin following DNA replication, so we examined the relative importance of Rtt106 and PCNA unloading for chromatin reassembly following DNA replication. We find that the major cause of the chromatin assembly defects of an elg1 mutant is PCNA retention on DNA following replication, with Rtt106-Elg1 interaction potentially playing a contributory role.

2018-10-31 | E-MTAB-6985 | biostudies-arrayexpress

Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and enhanced cysteine metabolic pathways

Project description:Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic protein aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared the skeletal muscle proteome and 3 h post-exercise transcriptome of gluteal muscle in MFM and control Arabian horses using iTRAQ and RNA-sequencing analyses. Differential expression (DE) was evaluated using edgeR and pathway analysis using Cytoscape and Cluego. Proteome analysis revealed significantly lower antioxidant peroxiredoxin 6 content (PRDX6, ↓4.14 log2 fold change [FC]), sarcomere protein tropomyosin (TPM2, ↓3.24x) and higher fatty acid transport enzyme carnitine palmitoyl transferase (CPT1B, ↑3.49x) in MFM vs. control muscle at rest. Three hours after exercise, 191 genes were DE in MFM vs. control muscle with a remarkably focused > 1.5 log2FC in genes involved in sulfur compound/ cysteine metabolism such as cystathionine-beta-synthase [CBS, ↑4.51] and a cysteine and neutral amino acid membrane transporter [SLC7A10, ↑1.79]. In MFM vs. control at rest, 284 genes were DE with > 1.5 log2 FC in pathways for structure morphogenesis, fiber organization, tissue development and cell differentiation including> 2 log2 FC in alpha actin-cardiac [↑ ACTC1], cytoskeletal desmoplakin [↑ DSP], basement membrane usherin [↓ USH2A] and delta like non-canonical Notch ligand 1, [↓ DLK1]. In conclusion, myofibrillar disarray and protein aggregation in MFM horses was embodied by DE expression in pathways of structure/fiber organization and tissue regeneration. Reduced antioxidant capacity as a potential etiology for MFM was supported by diminished cysteine rich antioxidant peroxiredoxin 6 with compensatory increased cysteine synthesis following exercise.

2019-11-12 | PXD009362 | Pride

Adaptation-dependent alterations in the human skeletal muscle proteome and phosphoproteome of human skeletal muscle in response to damaging resistance exercise

Project description:Resistance exercise (RE) enhances strength, muscle mass, and overall health. Intense RE also triggers rapid muscle damage that is efficiently restored through proteostatic mechanisms in healthy individuals. However, the specific factors and signalling processes active at sites of damage remain poorly understood. In this study, human subjects underwent acute, recurring, and interrupted high-intensity RE to induce, adapt, and deadapt skeletal muscle. Muscle biopsies were taken at thee time points to analyse the skeletal muscle proteome's localization and phosphorylation under these conditions. RE-induced lesions were reduced through continued training but quickly reestablished upon detraining.

2026-04-28 | PXD044976 | Pride

Bi-allelic variants of FILIP1 cause a congenital syndrome defined by facial dysmorphisms and a broad range of neurological manifestations

Project description:Filamin-A-interacting protein 1 (FILIP1) is a structural protein known to take on roles in neuronal and muscle function and integrity and to interact in addition to filamin-A with filamin-C. For both proteins pathogenic variants in the corresponding genes were linked to neurological symptoms and dysmorphisms (FLNA) or muscular diseases (FLNC) characterized by myofibrillar perturbations. Here, we report on five patients from four unrelated consanguineous families with homozygous FILIP1 variants (two nonsense and two missense) leading to a broad spectrum of neurological symptoms including brain malformations, neurodevelopmental delay as well as muscle weakness and pathology complicated by dysmorphic features shared among patients. Microscopic studies on the muscle biopsy derived from one patient harbouring a missense variant revealed core-like zones of myofibrillar disintegration, autophagic vacuoles and accumulation of FLNc thus introducing FILIP1 as a novel candidate gene of myofibrillar myopathies. Further functional studies confirmed the altered stability of this p.[Pro1133Leu] missense-mutant FILIP1 protein. Proteomic studies on the fibroblasts derived from the same patient revealed a dysregulation of a variety of proteins including FLNc, a biochemical finding which might accord with the manifestation of certain symptoms associated with the syndromic phenotype of FILIP1opathy.

2024-05-23 | PXD036407 | Pride

ChIP-seq to investigate the role of FliA-transcribed protein coding genes in Salmonella Typhimurium

Project description:FliA in S. Typhimurium directs transcription of large numbers of unstable, non-coding RNAs from intragenic promoters. Also in this study, we identify two previously unreported FliA-transcribed protein coding genes, including sdiA, which encodes a transcription factor that responds to quorum sensing signals produced by other bacteria.

2020-09-09 | E-MTAB-9503 | biostudies-arrayexpress

First Clinical and Myopathological Description of a Myofibrillar Myopathy with Congenital Onset and Homozygous Mutation in FLNC

Project description:Filamin C (encoded by the FLNC gene) is a large actin-cross-linking protein involved in shaping the actin cytoskeleton in response to signaling events both at the sarcolemma and at myofibrillar Z-discs of cross-striated muscle cells. Multiple mutations in FLNC are associated with myofibrillar myopathies of autosomal dominant inheritance. Here, we describe a boy with congenital onset of generalized muscular hypotonia and muscular weakness, delayed motor development but no cardiac involvement associated with a homozygous FLNC mutation affecting the rod domain of the protein. To demonstrate pathogenicity of this homozygous FLNC-mutation described, ultra-morphological, proteomic and functional investigations were performed in addition to immunological studies of known marker proteins for dominant filaminopathies. Our results showed that the mutant protein is expressed to similar quantities as the wildtype variant in control skeletal muscle fibres, alters the proteomic signature of quadriceps muscle, and results in the presence of ultrastructural perturbations. Moreover, comparable findings for filaminopathy marker proteins were found in both, our homozygous and a dominant case. The mutant protein is less stable and more prone to degradation by proteolytic enzymes than the wildtype variant. These combined findings extend the currently recognized clinical, genetic and biochemical spectrum of filaminopathies. The unusual congenital presentation of the disease indicates that homozygosity for a mutation in filamin C severely aggravates the phenotype.

2020-07-24 | PXD016657 | Pride

Transcriptomic profiling of chondrocytes and tenocytes in de- and re-differentiation relative to native tissue

Project description:De- and re-differentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and re-differentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion, and the expression of key developmental markers, challenges the physiological relevance of this culture system.

2016-06-01 | E-MTAB-4800 | biostudies-arrayexpress

Spatial proteomics of skeletal muscle using thin cryosections reveals metabolic adaption at the muscle-tendon transition zone

Project description:Morphological studies of skeletal muscle tissue have provided detailed insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix. However, a spatial proteomics analysis of the skeletal muscle, including the muscle-tendon transition zone, is lacking. Here, we prepared thin cryotome muscle sections along the longitudinal axis of the mouse soleus muscle and measured each muscle slice using short LC-MS gradients. We generated more than 3000 high-resolution longitudinal protein profiles of central to distal skeletal muscle regions and created a molecular network of different skeletal muscle regions that reveals the complex architecture of the muscle-tendon transition zone. Among the proteins that show an increasing profile from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the synthesis of extracellular matrix proteins, including collagen and fibronectin. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.

2024-05-22 | PXD046596 | Pride

Chip-chip from E. coli MG1655 cells with different methods to detect SeqA and σ32 binding and causes of high background

Project description:Reinvestigation of the chromatin immunoprecipitation procedure led us to discover four causes of high background: non-unique sequences, incomplete reversion of crosslinks, washing with spin-columns and insufficient RNase treatment. We used a publishd method giving a high background signal and a modified chromatin immunoprecipitation method which could greatly reduce the false positive rate and apply it to analyze genome wide binding of SeqA and σ32 binding in E. coli. RNA polymerase binding in wt E. coli MG1655 with old method (two biological relpicates); comparison of SeqA-binding to wt with old and modified method (two biological replicates each); comparison of SeqA-binding with old and modified method to E. coli ΔseqA (one array each); comparison of crosslinked/reversed to non crosslinked E. coli chrom. DNA; σ32 binding at 30°C and 43°C (two biological replicates each); σ32 binding at 30°C and 43°C with shortened RNase digestion during ChIP (one array each).

2010-07-12 | E-GEOD-19053 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data