Analysis of mouse liver secretome and proteome during nonalcoholic steatohepatitis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Liver
DISEASE(S): Non-alcoholic Steatohepatitis
SUBMITTER: 
Benjamin Parker
LAB HEAD: Benjamin Parker
PROVIDER: PXD024673 | Pride | 2022-02-27
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 191224_Magda_MM-307_CHOL_1.raw | Raw | |||
| 191224_Magda_MM-307_CHOL_6.raw | Raw | |||
| 191224_Magda_MM-307_CHOL_7.raw | Raw | |||
| 191224_Magda_MM-307_CHOL_8.raw | Raw | |||
| 191224_Magda_MM-307_CHOL_control1.raw | Raw |
Items per page: 5 1 - 5 of 57 |
Similar Datasets
Project description:Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogated hepatocyte protein secretion in two models of murine NASH to reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism. We identify arylsulfatase A (ARSA) as a novel hepatokine that is upregulated in NASH and type 2 diabetes. This submission contains proteomic analysis of quadracep lipid rafts with or without overexpression of ARSA.
2022-02-27 | PXD026280 | Pride
Project description:This project aims to analyse the proteins of outer membrane vesicles (OMVs) released by a Serratia bacteria strain Su_YN1, which is isolated from field-caught mosquito gut. Su_YN1 produces massive OMVs under host serum induction. The data contain LC-MSMS results of the OMVs released without serum induction (WT-), and serum induced OMVs of WT strain (WT+) and several gene disruption strains (disruption of the ABC transporter genes ABC1 and ABC2). This project was conducted by CEMPS lab and Shanghai hoogen biotech co.ltd. The CEMPS lab prepared the purified OMV samples and Shanghai hoogen biotech co.ltd conducted the LC-MSMS analysis.
2023-08-02 | PXD042831 | Pride
Project description:RNA splicing and the ubiquitin system allow the functional proteome to adapt in response to changing cellular contexts. However, the regulatory mechanisms connecting these processes remain poorly understood. Here we show that the deregulation of the spliceosome B complex caused by USP39 deficiency leads to a novel splicing profile characterized by the use of cryptic 5′splice sites. Importantly, disruptive variants evade mRNA surveillance pathways and are translated into topologically incorrect proteins. These cryptic isoforms disrupt proteostasis and activate the unfolded protein response, causing ER stress-induced cell death. Human cells respond to this proteotoxicity by enhancing ubiquitin-mediated proteolysis and ER-phagy. Our findings show how cell death triggered by cryptic splicing can be mitigated, and provide insight into the molecular pathogenesis of diseases such as retinitis pigmentosa.
2024-09-26 | PXD041509 | Pride
Project description:Non-alcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease worldwide, with 25% of these patients developing nonalcoholic steatohepatitis (NASH). NASH significantly increases the risk of cirrhosis and decompensated liver failure. Past studies in rodent models have shown the knockout of glycine-N-methyltransferase (GNMT) results in rapid pro-gression of steatosis, fibrosis, and hepatocellular carcinoma. However, the attenuation of GNMT in subjects with NASH and the molecular basis for its impact on the disease process are still unclear. To address this knowledge gap, we show the reduction of GNMT protein levels in the liver of NASH subjects compared to healthy controls. To gain insight into the impact of decreased GNMT in the disease process, we performed global label-free proteome studies on the livers from a murine Western diet-based model of NASH. Histological and molecular characterization of the animal model demonstrate high resemblance to the human disease.
2022-04-04 | PXD030781 | Pride
Project description:Autophagy facilitates the degradation of cellular content via the lysosome and is involved in cellular homeostasis and stress response pathways. As such, malfunction of autophagy is linked to a variety of diseases ranging from organ specific illnesses like cardiomyopathy to systemic illnesses such as cancer or metabolic syndromes. Given the variety of autophagic functions within a cell and tissue, regulation of autophagy is complex and contains numerous positive and negative feedback loops. While our knowledge of mechanisms for cargo selectivity has significantly improved over the last decade, our understanding of signaling routes activating individual autophagy pathways remains rather sparce. In this resource study, we report on a well-characterized chemical library assembled within the IMI initiative EUbOPEN containing 77 GPCR-targeting ligands that was used to systematically analyze LC3B-based autophagy as well as ER-phagy flux upon compound treatment. The global impact of hit compounds TC-G 1004, BAY 60-6583, PSNCBAM-1, TC-G 1008, LPA2 Antagonist 1, ML154, JTC-801 and ML-290 targeting Adenosine receptor A2a (ADORA2A), Adenosine receptor A2b (ADORA2B), Cannabinoid receptor 1 (CNR1), G-protein coupled receptor 39 (GPR39), Lysophosphatidic acid receptor 2 (LPAR2), neuropeptide S receptor 1 (NPSR1), NOP (OPRL1), and Relaxin receptor 1 (RXFP1) were subsequently analyzed and compared by TMT-based mass spectrometry. Our results indicate the differential impact of targeted GPCRs on known autophagy-associated proteins.
2024-07-18 | PXD047645 | Pride
Project description:Leukemia cells instruct their surrounding bone marrow microenvironment (BMM) rendering it hospitable to leukemia cell survival. Conversely, how cells of the BMM influence leukemia progression is less well understood. Pleckstrin homology domain family M member 1 (PLEKHM1) serves as a hub between fusion and secretion of intracellular vesicles. Here, we performed TMT-based quantitative proteomics to investigate the proteome of BMM-derived leucocytesfrom mice lacking Plekhm1 compared to wild-type animals, which have been transplanted withBCR-ABL1-expressing bone marrow cells.
2023-01-16 | PXD027044 | Pride
Project description:While deleterious mutations are responsible for the vast majority of TBK1-linked ALS/FTD cases, the ALS/FTD causing missense mutation p.E696K leads to a selective loss of TBK1/optineurin binding. Knock-in of this specific missense mutation causes progressive autophagolysosomal dysfunction and an ALS/FTD-like phenotype in mice, while, as opposed to TBK1 deletion, RIPK/TNF-α-dependent necroptosis or overt inflammation are absent. Our results highlight the role of autophagolysosomal dysfunction as a therapeutic target in TBK1-ALS/FTD.
2024-03-19 | PXD050731 | Pride
Project description:Homeostatic scaling is a global form of synaptic plasticity used by neurons to adjust overall synaptic weight and maintain neuronal firing rates while protecting information coding. While homeostatic scaling has been demonstrated in vitro, a clear physiological function of this plasticity type has not been defined. Sleep is an essential process that modifies synapses to support cognitive functions such as learning and memory. Evidence suggests that information coding during wake drives synapse strengthening which is offset by weakening of synapses during sleep .Here we use biochemical fractionation, proteomics and in vivo two-photon imaging to characterize wide-spread changes in synapse composition in mice through the wake/sleep cycle. We find that during the sleep phase, synapses are weakened through dephosphorylation and removal of synaptic AMPA-type glutamate receptors (AMPARs) driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors (mGluR1/5), consistent with known mechanisms of homeostatic scaling-down in vitro. Further, we find that these changes are important in the consolidation of contextual memories. While Homer1a gene expression is driven by neuronal activity during wake, Homer1a protein targeting to synapses serves as an integrator of arousal and sleep need through signaling by the wake-promoting neuromodulator noradrenaline (NA) and sleep-promoting modulator adenosine. During sleep or periods of increased sleep need Homer1a enters synapses where it remodels mGluR1/5 signaling complexes to promote AMPAR removal. Thus, we have characterized widespread changes occurring at synapses through the wake/sleep cycle and demonstrated that known mechanisms of homeostatic scaling-down previously demonstrated only in vitro are active in the brain during sleep to remodel synapses, contributing to memory consolidation.
2017-02-13 | PXD004537 | Pride
Project description:DNA methylation profile for the samples from 143 prostate cancer patients are provided. DNA methylation profiling of 143 prostate cancer patients. *** Clinical data will be provided when the data are open to the public.
2015-12-31 | E-GEOD-55479 | biostudies-arrayexpress
Project description:This study aims to analyze and compare the post-translational modification differences between human plasma- and genetic recombination-derived human serum albumin (HSA) in clinical treatments in China. 6 different post-translational modifications, including acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation, were detected using pan-specific antibodies through Western blot. The samples, consisting of human plasma-derived HSA (pHSA) from six different manufacturers and recombinant HSA (rHSA) expressed in yeast and oryza sativa, underwent detection of types of post-translational modifications. 4D label-free PTMs quantitative proteomic analysis was conducted to detect N-glycosylation and the above-mentioned post-translational modifications in pHSA and rHSA samples, and analyze the differences in modification sites and levels. Through Western blot analysis, all six pHSA and two rHSA samples were positive in the band of albumin (66.5 kDa) for the six post-translational modifications. Further analysis using 4D label-free PTMs quantitative proteomics revealed 25 (29) acetylated, 30 (32) succinylated, 41 (50) malonylated, 15 (23) phosphorylated, 36 (30) beta-hydroxybutyrylated, and 27 (34) lactylated modification sites in pHSA and rHSA samples and no N-glycosylation modification sites. The analysis results identified 1 acetylation (ALB_K160), 2 beta-hydroxybutyrylation (ALB_K569, ALB_K426), 3 crotonylation (ALB_K264, ALB_K581, ALB_K560), and 15 phosphorylation specific modification sites in pHSA, as well as 3 crotonylation (ALB_K560, ALB_K562, ALB_K75), 1 succinylation (ALB_K490), and 23 phosphorylation specific modification sites in rHSA. In pHSA (rHSA), 2 (6) acetylation, 10 (12) succinylation, 0 (9) crotonylation, 1 (9) phosphorylation, 6 (0) beta-hydroxybutyrylation, and 0 (7) lactylation specific modification sites were found. Additionally, in the common modification sites of pHSA and rHSA, pHSA showed up-regulation of amberylation (16:1) and beta-hydroxybutyrylation (12:2) in more sites, and up-regulation of acetylation (7:11), crotonylation (2:11), phosphorylation (1:8), and lactylation (1:14) in less sites compared to rHSA. In clinical treatment, the used pHSA and rHSA in China generally exhibit acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation, and there are differences in the site characteristics and modification levels of these modifications between pHSA and rHSA. Further experimental investigations are needed to explore the impact of post-translational modification differences on the biological function, efficacy, and safety of pHSA and rHSA.
2024-05-09 | PXD050752 | Pride