Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GHB analogs confer neuroprotection through specific interaction with the CaMKII hub domain

ABSTRACT: Ca2+/calmodulin-dependent protein kinase II alpha (CaMK2A) is an emerging drug target incerebral ischemia for which limited therapeutic options exist. Here we show that small-molecule analogs of the brain metabolite gamma-hydroxybutyric acid (GHB) afford neuroprotection via interaction specifically with the CaMK2A hub domain. Identification of CaMK2A as the GHB analog target was achieved by homogenate photoaffinity labeling followed by quantitative proteomics

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Ulrike Leurs

LAB HEAD: Jesper V. Olsen

PROVIDER: PXD019679 | Pride | 2021-07-22

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20170401_QE3_nLC05_ChKe_COLLAB_UL170.raw	Raw
	20170401_QE3_nLC05_ChKe_COLLAB_UL171.raw	Raw
	20170401_QE3_nLC05_ChKe_COLLAB_UL172.raw	Raw
	20170401_QE3_nLC05_ChKe_COLLAB_UL173.raw	Raw
	20170401_QE3_nLC05_ChKe_COLLAB_UL174.raw	Raw

Items per page:

1 - 5 of 17

Similar Datasets

CGH of Plasmodium falciparum selected with DSM1

Project description:Continual challenge of 107 ARMD Dd2 parasites with 0.3µM DSM1, a novel dihydroorotate dehydrogenase (DHODH) inhibitor, reproducibly generated ~5-fold resistance and 3-fold amplification of 30-100Kb DNA, always including the DHODH gene. Subsequent 3-10µM DSM-1 pressure selected for ~10-fold amplification of the copy number variant (CNV), and over 100-fold resistance. Target-specific and genome-wide DNA sequencing revealed no additional mutations contributing to DSM1 resistance. Each DSM1-resistant clone is compared to the Dd2 parent reference sample.

2013-05-01 | E-GEOD-37306 | biostudies-arrayexpress

Global hepatic transcript data from LRH-1 hep+/+ and LRH-1 hep-/- livers

Project description:Transcript data from LRH-1 hep+/+ and LRH-1 hep-/- livers from mice fed ad libitum and sacrificed at 7 am We used microarrays to detail the global programme of gene expression underlying hepatic function in ad libitum fed mice. 17-19-week-old mice were fed ad libitum, sacrificed at 7 am, and livers snap-frozen in liquid nitorgen for RNA extraction and hybridization on Affymetrix microarrays.

2014-07-11 | E-GEOD-59305 | biostudies-arrayexpress

Global hepatic transcript data from LRH-1 WT and LRH-1 K289R jejunums

Project description:Transcript data from LRH-1 WT and LRH-1 K289R jejunums from mice fed ad libitum and sacrificed at 7 am We used microarrays to detail the global programme of gene expression underlying jejunal function in ad libitum fed mice. 19-21-week-old mice were fed ad libitum, sacrificed at 7 am, and jejunums snap-frozen in liquid nitorgen for RNA extraction and hybridization on Affymetrix microarrays.

2014-07-11 | E-GEOD-59303 | biostudies-arrayexpress

Global transcript analysis of livers and/or jejunums of liver-specific Lrh-1 knockout as well as Lrh-1 K289R knockin mice

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-07-11 | E-GEOD-59333 | biostudies-arrayexpress

Effect of GnRH on miRNA expression in LbetaT2 cells

Project description:Mouse immortalized LbetaT2 gonadotrope cells treated with 100 nM GnRH for 2 h. GnRH treated LbetaT2 cells vs. untreated to assess whether GnRH regulates miRNA expression acutely. Treated and untreated RNA labeled independently then hybridized together to 2-color array. Duplicate arrays run with RNA from independent experiments.

2011-02-18 | E-GEOD-27398 | biostudies-arrayexpress

ADAP promotes effector cytokine release, degranulation and migration 1 of NK cells primed during in vivo Listeria monocytogenes infection in 2 mice

Project description:is involved in the formation of immune signaling complexes. To date only limited and moreover 35 conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we 36 investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular 37 pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed 38 impaired expression of IFN-γ and chemokines as well as impaired cytotoxic capacity in NK cells 39 lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin 40 production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular 41 distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells 42 did not uncover obvious differences in protein composition during the steady state and moreover, 43 similar early response patterns were induced in NK cells upon infection independent of the genotype. 44 In line with protein network analyses that suggested an altered migration phenotype in naïve 45 ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naïve 46 as well as infection-primed ADAPko NK cells compared to wild type NK cells. We propose that this 47 migration defect might account at least in part for the fact that during in vivo infection significantly 48 lower numbers of ADAPko NK cells accumulate in the spleen i.e. the site of infection. In conclusion, 49 we show here that during systemic Lm infection in mice ADAP is essential for efficient cytokine and 50 chemokine production, cytotoxic capacity and migration of NK cells.

2020-05-27 | PXD016305 | Pride

DIA-based systems biology approach unveils novel E3-dependent responses to a metabolic shift

Project description:Yeast Saccharomyces cerevisiae is a powerful model system for systems-wide biology screens and large-scale proteomics methods. The proteomics community has achieved nearly complete coverage for this organism owing to advances in mass spectrometry. However, it remains challenging to scale the technology for rapid and high-throughput analysis of the yeast proteome to investigate biological pathways on a global scale. Here we describe a systems biology approach employing plate-based sample preparation and rapid, single-run data independent mass spectrometry analysis (DIA). Our approach is straightforward, easy to implement and enables quantitative profiling and comparisons of hundreds of largely covered yeast proteomes in only a few days. We evaluate its capability by characterizing changes in the yeast proteome in response to a variety of stresses commonly used in yeast research, identify distinct responses to each stress, and provide a comprehensive resource of these responses. Using our facile, rapid and robust methodology, we observe many previously characterized stress responses, including carbon source dependent regulation of the GID E3 ligase, an important regulator of cellular metabolism during the switch between gluconeogenic and glycolytic growth conditions. Furthermore, we applied our methodology to search for new regulatory targets of the GID ligase during a metabolic switch. We are able to pinpoint effects of a single deletion or point mutation in the GID complex on the global proteome, and thereby identify and validate novel targets of the GID E3 ligase. Moreover, our approach allowed the identification of targets from multiple cellular pathways that display distinct patterns of regulation.

2020-11-26 | PXD021559 | Pride

GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain.

Project description:Ca2+/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) is a key neuronal signaling protein and an emerging drug target. The central hub domain regulates the activity of CaMKIIα by organizing the holoenzyme complex into functional oligomers, yet pharmacological modulation of the hub domain has never been demonstrated. Here, using a combination of photoaffinity labeling and chemical proteomics, we show that compounds related to the natural substance γ-hydroxybutyrate (GHB) bind selectively to CaMKIIα. By means of a 2.2-Å x-ray crystal structure of ligand-bound CaMKIIα hub, we reveal the molecular details of the binding site deep within the hub. Furthermore, we show that binding of GHB and related analogs to this site promotes concentration-dependent increases in hub thermal stability believed to alter holoenzyme functionality. Selectively under states of pathological CaMKIIα activation, hub ligands provide a significant and sustained neuroprotection, which is both time and dose dependent. This is demonstrated in neurons exposed to excitotoxicity and in a mouse model of cerebral ischemia with the selective GHB analog, HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid). Together, our results indicate a hitherto unknown mechanism for neuroprotection by a highly specific and unforeseen interaction between the CaMKIIα hub domain and small molecule brain-penetrant GHB analogs. This establishes GHB analogs as powerful tools for investigating CaMKII neuropharmacology in general and as potential therapeutic compounds for cerebral ischemia in particular.

| S-EPMC8346900 | biostudies-literature

MiR-210 is induced by Oct-2, regulates B-cells and inhibits autoantibody production

Project description:MicroRNAs are small, non-coding RNAs that regulate gene expression post-transcriptionally. Here, we show that miR-210 is induced by Oct-2, a key transcriptional mediator of B-cell activation. Germline deletion of miR-210 results in the development of autoantibodies from 5 months of age. Overexpression of miR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice over-expressing miR-210 exhibited impaired class-switched antibody responses, a finding confirmed in wild-type B-cells transfected with a miR-210 mimic. In vitro studies demonstrated a defect in cellular proliferation and cell-cycle entry, which was consistent with the transcriptomic analysis demonstrating down-regulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of miR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production. Splenic B-cells from different mouse strains were stimulated with either anti-IgM, CD40L and IL-4 or LPS for 48 hours Treatments: rest (unstimulated), Fab/Fab2 (=anti-IgM + CD40L + IL-4), LPS. There is no difference between Fab and Fab2 stimulation conditions. The goal of this study was to look for activation-induced microRNA changes upon B-cell activation, of which miR-210 was one of them.

2013-06-21 | E-GEOD-48186 | biostudies-arrayexpress

Phosphoproteomic profiling of hippocampus from offspring rats exposed to prenatal stress

Project description:Prenatal stress (PS) could cause depression of offprsing. Here, relative quantitative phosphoproteomics of hippocampus of PS-S and CON offspring rats were performed using LC-MS/MS to confirm known pathways and identify new areas of depression. A total of 6,790 phosphopeptides, 9,817 phosphorylation sites and 2978 phosphoproteins were detected. Among the 2978 phosphoproteins, 1760 (59.09%) with more than two phosphorylated sites, ENSRNOP00000023460 protein has more than 117 phosphorylated sites, and the average distribution of modification sites per 100 amino acids was 2.97. There were 197 different phophpeptides, including 140 increased phosphopeptides and 57 decreased phosphopeptides in PS-S offspring rats when compared to the CON offspring rats. These differential phosphopeptides corresponded to 100 upregulated and 44 downregulated phosphoproteins respectively. GO enrichment analysis these different phosphoproteins in the first five enrichments of CC category, MF category and BP category were involved in a total of 35 different phosphoproteins and these phosphoproteins were mainly related to myelin, microtubule and synapse associated proteins. The first five enrichment of KEGG pathways were found to be involved in many essential biological pathways, and the first five pathways included amphetamine addiction, insulin secretion, cushing syndrome and circadian entrainment signaling pathway. And these first five pathways were related to nine proteins including Adcy9, Apc, Cacna1c, Camk2a, Camk2b, Camk2g, Ctnnd2, Grin2a, Stx1a. Further research is needed to understand the precise role of these pathways in the depressive-like behavior of offspring rats caused by PS.

2021-12-30 | PXD019117 | Pride

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