Label free quantitative proteomics for determining the biological characterastic of eukaryocyte with or without BHB.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cervical Cancer Cell Line, Epithelial Cell Of Cervix
DISEASE(S): Cervical Cancer
SUBMITTER: 
siyu wang
LAB HEAD: Kai Zhang
PROVIDER: PXD051685 | Pride | 2025-07-04
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| BHB-1.raw | Raw | |||
| BHB-2.raw | Raw | |||
| BHB-3.raw | Raw | |||
| Control-1.raw | Raw | |||
| Control-2.raw | Raw |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Beta-hydroxybutyrate (BHB) is a ketone body whose signaling effects are not well characterized. The Newman Lab has observed a shift in brain cellular protein solubility following BHB treatment in vitro and in vivo. In the brains of C57BL/6 mice that received a 7-day oral gavage of ketone ester, we have observed formation of insoluble aggregates compared to control (canola oil). In a separate analysis, we treated soluble neuronal lysate from older C57BL/6 mice with multiple concentrations of R-BHB, then separated the proteins which become insolubilized. Here we seek to understand the composition of these insoluble aggregates by mass spectrometry and which proteins remain soluble, as a function of R-BHB treatment concentration.
2023-03-20 | MSV000091514 | MassIVE
Project description:Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB). However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we report impaired production of BHB in humans with SARS-CoV-2-induced but not influenza-induced acute respiratory distress syndrome (ARDS). BHB promotes the survival and the production of Interferon-g from CD4+ T cells. Using metabolic tracing analysis, we uncovered that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but can be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we find that ketogenic diet (KD) reduced pulmonary fibrosis, a feature particular pronounced in COVID-19 ARDS and delivery of BHB as ketone ester drink reduces the mortality of SARS-CoV-2 infected mice. Altogether, our data suggest that impaired ketogenesis in patients with SARS-CoV-2 infection accounts, at least partially for disease progression and that supplementation ketone ester might represent an easy-to-implement treatment to improve the clinical outcome of COVID-19 patients.
2022-07-01 | GSE207077 | GEO
Project description:Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging.
2024-01-31 | GSE253612 | GEO
Project description:In Alzheimer’s disease, dysfunctional microglia possess abnormal immunometabolic features that cause neuronal/synaptic damage and aggravate pathology. A critical question is how to reverse or fine-tune abnormal microglial metabolism towards beneficial immunometabolic outcomes. A major metabolic intervention strategy to raise circulating ketone levels for health benefits, such as by consumption of a ketogenic diet 1, fasting, or other approaches collectively called ketotherapeutics, has raised a great deal of interest, but its effects on microglia are not well understood. Our previous in vitro study showed that β-hydroxybutyrate (BHB), a major ketone body, reverses multiple pathological features of amyloid-β oligomer (AβO)-activated human microglia. In the current study, we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer’s disease mouse model. To capture the metabolic impact of BHB on microglia, we employed a “subacute” 1-week regimen of daily intraperitoneal injection of BHB (250 mg/kg), which induced brief and mild episodic (daily) ketosis. This short regimen was able to mitigate pro-inflammatory microglia activation linked to NLRP3 inflammasome formation, and reduce brain amyloid-β deposition by enhancing phagocytosis. Remarkably, this regimen mitigated the deficits of hippocampal long-term depression but not long-term potentiation, and this effect was linked to suppression of the inflammasome-generated cytokine IL-1β. Our results suggest that short-term BHB treatment may ameliorate microglial abnormalities and microglia-regulated synaptic deficits in Alzheimer’s disease. Because beneficial results were achieved with mild episodic BHB elevation alone without diet restriction and without the need of feeding a KD, our results have significant implications to human ketotherapeutics. As KDs are known for poor compliance and low sustainability due to their restrictive nature, our study opens the possibility for alternative ketogenic approaches that are less restrictive, potentially safer, and easier for compliance than a KD, such as short-term BHB injections or dietary ketone esters, a translatable form of induced ketosis.
2024-08-31 | GSE269488 | GEO
Project description:Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. BHB actively regulates gene expression and inflammatory activation through non-energetic signaling pathways. Neither of these activities has been well-characterized in the brain and they may represent mechanisms by which BHB affects brain function during aging. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We observed via flow cytometry that KD also modulates age-related systemic T cell functions. Next, we investigated whether BHB affects brain cells transcriptionallyin vitro. Gene expression analysis in primary human brain cells (microglia, astrocytes, neurons) using RNA-seq shows that BHB causes a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced LPS-induced inflammatory gene activation in microglia. Furthermore, we confirmed that BHB similarly reduces LPS-induced inflammation in primary mouse microglia and bone marrow-derived macrophages (BMDMs). BHB is recognized as an inhibitor of histone deacetylase (HDAC), an inhibitor of NLRP3 inflammasome, and an agonist of the GPCR Hcar2. Nevertheless, in microglia, BHB's anti-inflammatory effects are independent of these known mechanisms. Finally, we examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging. In summary, our findings demonstrate that BHB mitigates the microglial response to inflammatory stimuli, like LPS, possibly leading to decreased chronic inflammation in the brain after long-term KD treatment in aging mice.
2024-01-31 | GSE252513 | GEO
Project description:It is well established that EZH2, a lysine methyltransferase, is upregulated in most of aggressive cancers, highlighting the importance of EZH2 in cancer progression. Recent research has shown that metabolic reprogramming is pivotal in various biological processes, including cancer. Despite this, evidence of EZH2's role in regulating cancer metabolism remains limited. Our study reveals a negative correlation between EZH2 and HMGCS2, a gene belongs to the HMG-CoA synthase, in prostate and breast cancers. Furthermore, HMGCS2 is inversely related to cancer progression and prognosis in these cancers and is epigenetically repressed by EZH2 both in vitro and in vivo. Notably, restored EZH2 reduces the elevated HMGCS2 levels observed upon EZH2 depletion. Overexpression of HMGCS2 decreases tumorigenesis in both prostate and breast cancers. Additionally, β-hydroxybutyrate (BHB), a downstream metabolite of HMGCS2, impedes prostate cancer progression by targeting EZH2 via direct protein-compound interaction -mediated protein degradation. More importantly, ketone drink of BHB administration dramatically reduces tumor size and weight in a prostate cancer xenograft model. Combining ketone drink with FDA-approved drugs enzalutamide and Tazemetostat further suppresses tumor progression. Overall, EZH2- HMGCS2-BHB regulatory network plays a critical role in the progression of prostate cancer and ketone drink is a novel therapeutic tool for patients with aggressive prostate cancer.
2025-05-27 | GSE269259 | GEO
Project description:It is well established that EZH2, a lysine methyltransferase, is upregulated in most of aggressive cancers, highlighting the importance of EZH2 in cancer progression. Recent research has shown that metabolic reprogramming is pivotal in various biological processes, including cancer. Despite this, evidence of EZH2's role in regulating cancer metabolism remains limited. Our study reveals a negative correlation between EZH2 and HMGCS2, a gene belongs to the HMG-CoA synthase, in prostate and breast cancers. Furthermore, HMGCS2 is inversely related to cancer progression and prognosis in these cancers and is epigenetically repressed by EZH2 both in vitro and in vivo. Notably, restored EZH2 reduces the elevated HMGCS2 levels observed upon EZH2 depletion. Overexpression of HMGCS2 decreases tumorigenesis in both prostate and breast cancers. Additionally, β-hydroxybutyrate (BHB), a downstream metabolite of HMGCS2, impedes prostate cancer progression by targeting EZH2 via direct protein-compound interaction -mediated protein degradation. More importantly, ketone drink of BHB administration dramatically reduces tumor size and weight in a prostate cancer xenograft model. Combining ketone drink with FDA-approved drugs enzalutamide and Tazemetostat further suppresses tumor progression. Overall, EZH2- HMGCS2-BHB regulatory network plays a critical role in the progression of prostate cancer and ketone drink is a novel therapeutic tool for patients with aggressive prostate cancer.
2025-05-27 | GSE269208 | GEO
Project description:Mammals evolved to withstand frequent fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally-regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this produces effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond to a following fasting bout profoundly differently from mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’, i.e. induced more strongly by fasting following ADF. Enhancers regulating these genes are also sensitized and harbor increased binding of the major ketogenic transcription factor. ADF mice show augmented ketogenesis and their sensitized enhancers are covalently marked with ketone body residues. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augmenting ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated environmental signals.
2024-11-18 | GSE212776 | GEO
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
Project description:Testicular aging commonly leads to testosterone deficiency and impaired spermatogenesis, yet the underlying mechanisms remain elusive. Here, a comprehensive analysis of senescence landscapes in mice testes during aging revealed that the Leydig cells (LCs) are particularly vulnerable to aging processes. Single-cell RNA sequencing identified the expression of Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2), the gene encoding the rate-limiting enzyme of ketogenesis, decreased significantly in LCs from aged mice. Additionally, the concentrations of ketone bodies β-hydroxybutyric acid (BHB) and acetoacetic acid (AcAc) in the young testes were substantially higher than that in serum, but significantly diminished in aged testes. Silencing of Hmgcs2 in young LCs resulted in decreased ketone body production, which in turn drove LCs senescence and accelerated testicular aging. Mechanistically, BHB acted as an endogenous inhibitor of histone deacetylase 1 to upregulate the expression of Foxo3a by promoting histone acetylation, thereby mitigating LCs senescence and promoting testosterone production. Consistently, enhanced ketogenesis by genetic manipulation or oral BHB supplementation alleviated LCs senescence and ameliorated testicular aging in aged mice. These findings highlight defective ketogenesis as a pivotal factor in testicular aging, suggesting novel therapeutic avenues for addressing age-related testicular dysfunction.
2025-03-27 | GSE287203 | GEO