Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

β-OHB Reduces Reinstatement of Cocaine Conditioned Place Preference Through Hippocampal CaMKII-α β-Hydroxybutyrylation

ABSTRACT: Studies have shown the therapeutic effects of a ketogenic diet (KD) on epilepsy, but the effect of KD on drug reinstatement is largely unclear. This study aims to investigate whether KD consumption possesses therapeutic potential for cocaine reinstatement and the molecular mechanism. We find that KD significantly reduce cocaine induced-reinstatement in mice, which is accompanied by a markedly elevated level of β-hydroxybutyrate (β-OHB), the most abundant ketone body, in the hippocampus. The underlying mechanism is that β-OHB posttranslationally modify CaMKII-α with β-hydroxybutyrylation, resulting in significant inhibition of T286 autophosphorylation and downregulation of CaMKII activity. Collectively, our results reveal that β-hydroxybutyrylation is a posttranslational modification of CaMKII-α that plays a critical role in mediating the effect of KD consumption in reducing cocaine reinstatement.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Hongchun Li

LAB HEAD: Hongchun Li

PROVIDER: PXD037321 | Pride | 2022-11-30

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Proteome-wide analysis and functional identification of lysine β-hydroxybutyrylation in Ustilaginoidea virens

Project description:Lysine β-hydroxybutyrylation (Kbhb) is an evolutionarily conserved and widespread post-translational modification (PTM) in active gene transcription and cellular proliferation. However, its function remains unknown in phytopathogenic fungi. Here, we report a comprehensive identification of Kbhb in the rice false smut fungus Ustilaginoidea virens. Total 2,204 Kbhb sites were identified in 852 proteins. We found that β-hydroxybutyrylated proteins were enriched in mannose type O-glycan biosynthesis, citrate cycle (TCA cycle), ribosome, glycolysis/gluconeogenesis, proteasome, glyoxylate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, pyruvate metabolism, biosynthesis of nucleotide sugars, butanoate metabolism, arginine biosynthesis, fructose and mannose metabolism, propanoate metabolism, methane metabolism, fatty acid degradation, β-alanine metabolism, valine, leucine and isoleucine degradation, phagosome, oxidative phosphorylation pathway. This suggests Kbhb might be involved in basic life functions of Ustilaginoidea virens.

2023-10-24 | PXD039304 | Pride

mPFC DUSP1 mediates adolescent cocaine exposure-induced higher sensitivity to drug in adulthood

Project description:Adolescent cocaine abuse increases the risk for developing addiction in later life, but the underlying molecular mechanism remains poorly understood. Here, we establish adolescent cocaine-exposed (ACE) male mouse models. A subthreshold dose of cocaine (sdC) treatment, insufficient to produce conditioned place preference (CPP) in adolescent mice, induces CPP in ACE mice during adulthood, along with more activated CaMKII-positive neurons, higher dual specificity protein kinase phosphatase-1 (Dusp1) mRNA, lower DUSP1 activity, and lower DUSP1 expression in CaMKII-positive neurons in the medial prefrontal cortex (mPFC). Overexpressing DUSP1 in CaMKII-positive neurons suppresses neuron activity and blocks sdC-induced CPP in ACE mice during adulthood. On the contrary, depleting DUSP1 in CaMKII-positive neurons activates more neurons and further enhances sdC-induced behavior in ACE mice during adulthood. Also, ERK1/2 might be a downstream signal of DUSP1 in the process. Our findings reveal a role of mPFC DUSP1 in ACE-induced higher sensitivity to the drug in adult mice. DUSP1 might be a potential pharmacological target to predict or treat the susceptibility to addictive drugs caused by adolescent substance use.

2023-05-20 | GSE231074 | GEO

Quantitative Proteomics Analysis Expands the Roles of Lysine -Hydroxybutyrylation Pathway in Response to Environmental β-Hydroxybutyrate

Project description:Lysine -hydroxybutyrylation (Kbhb) is a newly identified protein post-translational modification that derived from the ketone body β-hydroxybutyrate (BHB). BHB is synthesized in the liver from fatty acids and could be delivered to peripheral tissues when the supply of glucose is too low for the body’s energetic needs. The plasma concentration of BHB can increase up to 20 mM during starvation and in pathological conditions. Despite the progresses, how the cells that do not produce BHB respond to elevated environmental BHB remains largely unknown. Given that BHB significantly drives Kbhb, here we performed a quantitative proteomics study to characterize the BHB-induced lysine -hydroxybutyrylome and acetylome. A total of 840 unique Kbhb sites across 429 proteins were identified, with 42 sites from 39 proteins being increased by more than 50% in response to BHB. The upregulated β-hydroxybutyrylome induced by BHB are involved in aminoacyl-tRNA biosynthesis, 2-oxocarboxylic acid metabolism, citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and pyruvate metabolism pathways. Moreover, some BHB-targeted Kbhb substrates are potentially linked to diseases such as cancer. Taken together, this study revealed the dynamics of lysine -hydroxybutyrylome and acetylome in response to environmental BHB, which sheds light on the roles for Khib in regulation of diverse cellular processes and provides new insights into the biological functions of BHB.

2022-04-04 | PXD029481 | Pride

Expression data from isoalted adult cardiomyocytes w/o Isopretrenol stimulation.

Project description:Sympathetic activation of β-adrenergic receptors (β-AR) represent a hallmark in the development of heart failure (HF). Genome-wide analysis of CaMKII-mediated H3S28p in response to chronic β-AR stress by chromatin-immunoprecipitation followed by massive genomic sequencing led to the identification of CaMKII-dependent H3S28p target genes.40 % of differentially H3S28p-enriched genomic regions were associated with differential, mostly increased expression of the nearest genes, pointing to CaMKII-dependent H3S28p as an activating histone mark.

2019-11-11 | GSE131796 | GEO

Regulation of mitochondrial Ca2+ uniporter expression and calcium signalling by lncRNA Tug1 in cardiomyocytes

Project description:Cardiomyocyte Ca2+ is buffered by mitochondria via the mitochondrial calcium uniporter (MCU) complex. The MCU complex consists of pore-forming proteins including the mitochondrial calcium uniporter (MCU), and regulatory proteins such as mitochondrial calcium uptake proteins 1 and 2 (MICU1/2). The stoichiometry of these proteins influences the sensitivity to Ca2+ and activity of the complex. However, the factors that regulate their gene expression remain incompletely understood. Long non-coding RNAs (lncRNAs) regulate gene expression through various mechanisms, and we recently found that the lncRNA Tug1 affected the expression of MCU-associated genes. To further explore this, we knocked down Tug1 (Tug1 KD) in H9c2 rat cardiomyocytes using antisense LNA oligo. This led to increased MCU protein expression yet this did not enhance a marker of mitochondrial Ca2+ uptake. RNA-seq revealed that Tug1 KD increased Mcu and led to differential expression of genes and pathways related to Ca2+ regulation in the heart. To understand the effect of this on Ca2+ signalling, we measured phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its downstream target cAMP Response Element-Binding protein (CREB), a transcription factor known to promote Mcu gene expression. Tug1 KD attenuated the increase in CAMKII and CREB phosphorylation in response to ionomycin, a Ca2+ ionophore. Inhibition of CaMKII, but not CREB, partially prevented the Tug1 KD mediated increase in Mcu. Together, these data suggest that Tug1 modulates MCU expression via a mechanism that may involve CAMKII and CREB. The Tug1 mediated regulation of MCU on mitochondrial Ca2+ uptake, may have functional consequences for cellular Ca2+ handling which could have implications for cardiac disease.

2023-07-22 | GSE237787 | GEO

GPR162 is a beta cell CART receptor [CART_KD]

Project description:Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knock down (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.

2023-10-20 | GSE245796 | GEO

GPR162 is a beta cell CART receptor [INS1_GPR162]

2023-10-20 | GSE245691 | GEO

Brain histone beta-hydroxy-butirylation couples metabolism with gene expression (ChIP-seq)

Project description:We report changes in beta-hydroxybutyrylation of lysine (K) 9 on histone H3 in the occipital cortex of mice after 48 hour fasting.

2023-08-21 | GSE168723 | GEO

Proteomes and Ubiquitylomes Analysis Reveals the Involvement of Ubiquitination in Protein Degradation in rosa hybrida during petal abscission.

Project description:We employed Non-standard quantitative techniques and quantitative proteomics techniques based on mass spectrometry to perform proteomics analyses for the petal abscission zone of rose petal at stage 3 stage 5. In total, 6595 proteins were detected, we compared differentially expressed proteins (DEPs) between stage 3 and stage 5 (FC>1.5, P-value<0.05). We found that 271 proteins were significantly up-regulated, while 444 proteins were significantly down-regulated.

2023-03-11 | PXD036665 | Pride

Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex

Project description:Abstract Background Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no FDA approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Methods Sprague-Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Results Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Conclusion Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multi-region discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.

2021-01-28 | PXD019485 | Pride

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