Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes

ABSTRACT: To elucidate the specific molecular signals associated with the activation or blockade of CB1 and CB2 receptors in this glial cell, mass spectrometry-based proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmacological stimuli: the phytocannabinoid cannabidiol (CBD); CB1 and CB2 agonists WIN55,212-2, ACEA, and HU308; CB1 and CB2 antagonists AM251 and AM630; and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oligodendrocyte Precursor Cell, Cell Culture

SUBMITTER: Bradley Smith

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD031923 | Pride | 2022-06-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes.

de Almeida Valéria V Seabra Gabriela G Reis-de-Oliveira Guilherme G Zuccoli Giuliana S GS Rumin Priscila P Fioramonte Mariana M Smith Bradley J BJ Zuardi Antonio W AW Hallak Jaime E C JEC Campos Alline C AC Crippa José A JA Martins-de-Souza Daniel D

European archives of psychiatry and clinical neuroscience 20220527 7

Cannabinoid signaling, mainly via CB1 and CB2 receptors, plays an essential role in oligodendrocyte health and functions. However, the specific molecular signals associated with the activation or blockade of CB1 and CB2 receptors in this glial cell have yet to be elucidated. Mass spectrometry-based shotgun proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmaco ...[more]

PMID: 35622101

Similar Datasets

RNA-seq of age-associated transcriptome changes in brown adipose tissue

Project description:Brown adipose tissue (BAT) plays a central role in energy homeostasis through non-shivering thermogenesis. Besides, recent human studies using 18FDG-PET/CT imaging demonstrated that BAT acts as a significant metabolic-sink for glucose. Notably, these functions in BAT decrease with age: however what regulates this process remains poorly understood. To this end, we employed RNA-seq to identify the transcriptional changes in BAT of young and old mice.

2019-07-20 | E-MTAB-7445 | biostudies-arrayexpress

Phosphoproteomic and functional approaches reveal changes in sperm-specific proteins downstream KOR in human spermatozoa

Project description:G-protein coupled receptors (GPCRs) belong to the seven transmembrane receptors superfamily that in response to external stimuli, transduce signals via G proteins to initiate different intracellular signaling pathways which culminate in specific cellular responses. Although in somatic cells the GPCR participate in a broad variety of physiological processes, the expression of diverse GPCRs at the plasma membrane of human spermatozoa suggests their involvement in the regulation of sperm fertility. Mature spermatozoa could present unique features in their molecular mechanisms downstream GPCRs due to the fact that they possess sperm-specific proteins and are transcriptionally and translationally silent. In order to decipher the signaling pathways engaged by this receptor superfamily in human spermatozoa, we selected the kappa-opioid receptor (KOR) as a study model and applied, for first time, phosphoproteomic approach based on TMT labeling and LC-MS/MS analyses combined with functional studies using a specific agonist of KOR, U50488H.

2019-01-11 | PXD011290 | Pride

Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

Project description:The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transport capabilities due to a variety of different membrane-associated transport proteins. However, DCT and CCD cells appear to be modulated via the same hormones. The objective of this study was assess the differential response of DCT and CCD cells to long-term exposure to the hormones vasopressin or angiotensin II, both of which modulate DCT and CCD cells differently. Mass spectrometry based quantitative proteomics was used to profile the differential proteome between DCT and CCD.

2017-12-15 | PXD005454 | Pride

Network analyses and data integration of proteomics and metabolomics from leaves of two contrasting varieties of sugarcane in response to drought

Project description:Uncovering the molecular mechanisms involved in the responses of crops to drought is crucial to understand and enhance drought tolerance mechanisms. Sugarcane (Saccharum spp.) is an important commercial crop cultivated mainly in tropical and subtropical areas for sucrose and ethanol production. Usually, drought tolerance has been investigated by single omics analysis (e.g. global transcripts identification). Here we combine label-free quantitative proteomics and metabolomics data (GC-TOF-MS), using a network-based approach, to understand how two contrasting commercial varieties of sugarcane, CTC15 (tolerant) and SP90-3414 (susceptible), adjust their leaf metabolism in response to drought. To this aim, we propose the utilization of regularized canonical correlation analysis (rCCA), which is a modification of classical CCA, and explores the linear relationships between two datasets of quantitative variables from the same experimental units, with a threshold set to 0.99. Light curves revealed that after four days of drought, the susceptible variety had its photosynthetic rate already significantly reduced, while the tolerant cultivar did not show major reduction. Upon twelve days of drought, the susceptible plants had the photosynthetic rate completely reduced, while the tolerant cultivar was at a third of its maximum. Our results provide a reference data set and demonstrate that rCCA can be a powerful tool to infer experimentally metabolite-protein or protein-metabolite associations to understand plant biology.

2020-01-02 | PXD014920 | Pride

Structural mechanism underlying primary and secondary coupling between GPCRs and the Gi/o family

Project description:G protein-coupled receptors (GPCRs) are the largest receptor superfamily that can propagate various extracellular stimulus into cells by coupling with heterotrimeric G proteins. G proteins are divided into four families, Gs, Gi/o, Gq/11 and G12/13, which are responsible for the transduction of discrete downstream signaling pathways. Interestingly, one receptor can couple to more than one G protein subtype with different coupling efficiency or kinetics; coupling with the highest efficiency and/or kinetics is known as ‘primary coupling’ whereas the one with lower efficiency and/or slower kinetics is known as ‘secondary coupling’. Due to its significance in human physiology, there has been a great effort to elucidate the precise mechanism of GPCR-G protein coupling, however, the complex nature of GPCR and G protein interaction raises more unanswered questions. Here, we utilized hydrogen/deuterium exchange mass spectrometry (HDX-MS) to understand the molecular mechanism underlying primary and secondary Gi/o coupling using muscarinic acetylcholine receptor type 2 (M2R) and β2-adrenergic receptor (β2AR) as the primary and secondary Gi/o-coupling receptors, respectively. Results showed the engagement of the distal C-terminus of Gi/o with the receptor differentiates primary and secondary Gi/o couplings. In addition, the interaction between the intracellular loop 2 (ICL2) of the receptor and Gi/o in primary Gi/o coupling is not as critical as in primary Gs coupling.

2020-07-02 | PXD019367 | Pride

Gene expression profiles from islets of a β-cell-specific CB1-knockout mice

Project description:The cannabinoid 1 receptor (CB1) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1 is expressed on pancreatic beta (β)-cells where its functions have not been fully described. We generated a β-cell-specific CB1-knockout (β-CB1-/-) mouse to study the long-term consequences of CB1 ablation on β-cell function in adult mice. β-CB1-/- mice had increased basal- and stimulated-insulin secretion and intra-islet cAMP levels, resulting in primary hyperinsulinemia, as well as increased β-cell viability, proliferation, and islet area. Hyperinsulinemia led to insulin resistance, which was aggravated by a high fat/high glucose diet and weight gain, although β-cells maintained their insulin secretory capacity in response to glucose. Strikingly, islets from β-CB1-/- mice were protected from diet-induced inflammation. Mechanistically we show that this is a consequence of curtailment of oxidative stress and reduced activation of Nlrp3 inflammasome in β-cells. Our data demonstrate CB1 to be a negative regulator of β-cells and a mediator of islet inflammation under conditions of metabolic stress.

2018-03-07 | GSE102027 | GEO

The comparison of exosomal miRNAs from ECM or media derived from HFF-CBD-Lamp2b cells, HFF cells, HFF-Lamp2b cells and hUCMSCs

Project description:The next-generation sequencing technology was used to investigate the difference of RNAs content among the different types of exosomes from the media of HFF cells, HFF-Lamp2b cells and hUCMSCs, and from the ECM of HFF-CBD-Lamp2b cells

2021-10-12 | E-MTAB-10905 | biostudies-arrayexpress

Genome-wide expression profiling revealed peripheral effects of CB1 inverse agonists in improving insulin sensitivity and metabolic parameters

Project description:Inhibition of cannabinoid receptor 1 (CB1) has shown efficacy in reducing body weight and improving metabolic parameters, with the effects correlating with target engagement in the brain. Recently, the peripheral effects of inhibiting the CB1 receptor has been appreciated through studies in diet-induced obese and liver-specific CB1 KO mice. In this report, we systematically investigated gene expression changes in peripheral tissues of DIO mice treated with the CB1 inverse agonist AM251. CB1 receptor inhibition led to down-regulation of genes within the de novo fatty acid and cholesterol synthetic pathways, including SREBP-1 and -2, and their downstream targets in both liver and adipose tissue. In addition, genes involved in fatty acid Beta-oxidation were up-regulated with AM251 treatment, probably through the activation of PPARalpha. In adipose tissue, CB1 receptor inhibition led to the down-regulation of genes in the TNFalpha signal transduction pathway and possibly to the activation of PPARgamma, both of which would result in improved insulin sensitivity.

2010-06-21 | GSE21069 | GEO

NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine

Project description:Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models amenable for studying the neurobiology of schizophrenia may contribute to fill the gaps led by the widely employed animal models. Here we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to resective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass- spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia.

2024-02-06 | PXD046944 | Pride

Role of myeloid cannabinoid CB1 receptor in atherosclerosis

Project description:Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cellspecific effects in this disease are not well understood. Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1 deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sexspecific differences in proliferation were dependent on estrogen receptor (ER)α estradiol signaling. Kinase activity profiling revealed a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further unveiled chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, hinting to a possible implication of CB1-dependent regulation in human pathophysiology. In conclusion, impaired macrophage CB1 signaling is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming. The importance of macrophage CB1 signaling seems to be more pronounced in male mice.

2023-12-07 | GSE249503 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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