Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cancer-derived branched-chain ketoacids modulate macrophage polarization and metabolic reprogramming

ABSTRACT: This study aims to uncover the effects of cancer-derived branched-chain ketoacids on macrophage polarization and the underlying mechanism. We uncovered the global responses of branched-chain ketoacids-stimulated macrophages by proteomics analysis. Functional enrihment analysis indicated that these ketoacids significantly altered macrophage metabolism, apoptosis and phagocytosis.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow, Macrophage

SUBMITTER: Zhengnan Cai

LAB HEAD: Wolfram Weckwerth

PROVIDER: PXD032100 | Pride | 2022-10-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Combined_BCKAs.xlsx	Xlsx
	G01DMEM.raw	Raw
	G02DMEM.raw	Raw
	G03AE.raw	Raw
	G07_AKIV.raw	Raw

Items per page:

1 - 5 of 17

Similar Datasets

Branched-chain ketoacids derived from cancer cells modulate macrophage polarization and metabolic reprogramming

Project description:<p>Macrophages are prominent immune cells in the tumor microenvironment that can be educated into pro-tumoral phenotype by tumor cells to favor tumor growth and metastasis. The mechanisms that mediate a mutualistic relationship between tumor cells and macrophages remain poorly characterized. Here, we have shown <em>in vitro</em> that different human and murine cancer cell lines release branched‐chain α‐ketoacids (BCKAs) into the extracellular milieu, which influence macrophage polarization in an monocarboxylate transporter 1 (MCT1)‐dependent manner. We found that α‐ketoisocaproate (KIC) and α‐keto‐β‐methylvalerate (KMV) induced a pro‐tumoral macrophage state, whereas α‐ketoisovalerate (KIV) exerted a pro‐inflammatory effect on macrophages. This process was further investigated by a combined metabolomics/proteomics platform. KMV and KIC altered macrophage tricarboxylic acid (TCA) cycle intermediates and increased polyamine metabolism. Proteomic and pathway analyses revealed that the three BCKAs, especially KMV, exhibited divergent effects on the inflammatory signal pathways, phagocytosis, apoptosis and redox balance. These findings uncover cancer‐derived BCKAs as novel determinants for macrophage polarization with potential to be selectively exploited for optimizing antitumor immune responses.</p>

2022-10-03 | MTBLS4497 | MetaboLights

Impact of Preoperative Oral Branched-chain Amino Acids on Reducing Postoperative Insulin Resistance.

Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery. There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.

| 2744698 | ecrin-mdr-crc

Codon-specific ribosome stalling reshapes translational dynamics during branched-chain amino acid starvation

Project description:Background: Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results: All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5' end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions: Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.

2025-09-02 | GSE291652 | GEO

Codon-specific ribosome stalling reshapes translational dynamics during branched-chain amino acid starvation

Project description:Background Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5′ end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.

2025-09-02 | GSE291653 | GEO

ACSS2-mediated acetylation promotes BCAT1 aggradation to elevate branched-chain amino acid metabolism and development of pancreatic cancer

Project description:ACSS2-mediated acetylation promotes BCAT1 aggradation to elevate branched-chain amino acid metabolism and development of pancreatic cancer

2025-05-01 | GSE279400 | GEO

Nervous system reduction in branched-chain amino acid metabolism disrupts hippocampal neurogenesis and memory

Project description:To study the role of branched-chain amino acid metabolism in neural stem cells we generated two primary neural stem cell culture lines in which on was deleted for the Ppm1k gene using floxed cells and adenovirus delviered cre-recombinase.

2023-04-06 | GSE205603 | GEO

Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Branched‐chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi‐omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin‐proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show a slower turnover of a GFP‐based proteasome substrate, which is suppressed by loss‐of‐function of the first BCAA catabolic enzyme, the branched‐chain aminotransferase BCAT‐1. The exogenous supply of BCAA‐derived carboxylic acids, which are known to accumulate in the body fluid of patients with BCAA metabolic disorders, is sufficient to regulate the UPS. The link between BCAA intermediates and UPS function presented here sheds light on the unexplained role of BCAAs in the aging process and opens future possibilities for therapeutic interventions.

2022-09-22 | GSE185451 | GEO

Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

| PRJNA769111 | ENA

Branched chain amino acid sufficiency is necessary for proper luteinizing hormone response, testosterone synthesis, and motor coordination

Project description:Loss of branched-chain α-keto acid dehydrogenase kinase (BCKDK) increases branched-chain amino acid (BCAA) oxidation by disinhibiting BCKDH. We previously observed that in Bckdk knockout (KO) mice circulating BCAA levels are significantly reduced, negatively affecting neurological function, motor behavior, and male fertility. This work comparatively assessed how systemic loss of Bckdk modulates the transcriptome in testes and skeletal muscle under control diet feeding. Freely-fed adult male C57BL6/J mice and Bckdk KO mice on the C57BL6/J genetic background were euthanized by decapitation at the mid-point of the light cycle and tissues were quickly harvested and frozen in liquid nitrogen. Total RNA was extracted from frozen testes and hind-limb muscle (gastrocnemius and plantaris combined).

2025-09-30 | GSE309126 | GEO

Short & branched-chain fatty acids analysis of mouse cecum by GCMS.

Project description:Short & branched-chain fatty acids analysis of mouse cecum by GCMS.

2023-10-10 | MSV000093076 | MassIVE