Acyl CoA binding protein as a potential driver of pathological aging.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1209892 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR31980443_1.fastq.gz | Fastqsanger.gz | |||
| SRR31980443_2.fastq.gz | Fastqsanger.gz | |||
| SRR31980444_1.fastq.gz | Fastqsanger.gz | |||
| SRR31980444_2.fastq.gz | Fastqsanger.gz |
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Project description:The tissue hormone acyl coenzyme A binding protein (ACBP, encoded by the gene diazepam binding inhibitor, DBI) has been involved in various facets of pathological aging. Here, we show that ACBP plasma concentrations are elevated in (close-to-)centenarians commensurate with their health deterioration, correlating with a reduced glomerular filtration rate and a surge in senescence-associated cytokines. In a mouse model of chronic kidney injury by cisplatin, we observed that ACBP neutralization by means of a monoclonal antibody (mAb) prevented histopathological and functional signs of organ failure. ACBP inhibition also prevented the senescence of tubular epithelial cells and glomerular podocytes induced by cisplatin or doxorubicin, respectively, as measurable by the immunohistochemical detection of cyclin dependent kinase inhibitor 1A (CDKN1A, best known as p21). Senescence was also blocked by anti-ACBP mAb in additional mouse models of accelerated aging. This applies to liver damage induced by a combination of high-fat diet and carbon tetrachloride, where hepatocytes become senescent. In addition, administration of anti-ACBP mAb prevented natural and doxorubicin-accelerated cardiomyocyte senescence. We performed single nucleus RNA sequencing to study the transcriptome of hearts that had been exposed to doxorubicin and/or anti-ACBP in vivo. In cardiomyocytes, doxorubicin caused the anti-ACBP-reversible dyregulation of mRNAs coding for cardioprotective proteins involved in autophagy, fatty acid oxidation, mitochondrial homeostasis and oxidative phosphorylation. Altogether, these findings plead in favor of a broad antiaging effect of ACBP neutralization across different organ systems.
2025-06-20 | GSE286549 | GEO
Project description:Acyl-coA Binding Protein neutralization improves cancer immunosurveillance
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Project description:The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergoes intramolecular catalysis to form reactive intermediates which non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized the protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the ‘acylomes’ of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation, and validated malate dehydrogenase as a key target. These data identify a fundamental relationship between reactive acyl-CoA species and proteins, and define a new regulatory paradigm in metabolism.
2017-04-11 | PXD005895 | Pride
Project description:5 day RNAi treatment to knockdown Enigma, CG9006, a Drosophila mitochondrial protein with homology to acyl-CoA dehydrogenases. Experiment Overall Design: Kc-167 cells, 5 day treatment with Enigma-specific RNAi or beta-lactamase control RNAi. Specifics:1.6X10^6 cells in 0.5mL of serum-free Sang's M3 media incubated for 1 hour with 20ug of dsRNA, subsequently equal volume of M3 media containing 10% serum was added. Cells harvested after 5 days. RNAi efficiency measured by immunoblot for Enigma.
2007-07-31 | E-GEOD-3566 | biostudies-arrayexpress
Project description:Acyl-CoAs are essential for life. These metabolites serve as fundamental cellular building blocks in the biosynthesis of lipids, intermediates in energy production via the TCA cycle, and essential precursors for reversible protein acetylation. Each of these roles are dependent on acyl-CoA/protein interactions, physical contacts that can regulate protein function via a variety of mechanisms. We utilized systems-level analyses to characterize novel protein networks that interact with metabolic acyl-CoAs, and evaluate the potential of these interactions to facilitate enzyme activity or non-enzymatic acylation. Our studies provide a roadmap for integrating chemoproteomic data with systems biology analysis, and establish a novel resource for understanding the diverse signaling roles of acyl-CoAs in biology and disease.
2019-11-21 | PXD013157 | Pride
Project description:Neutralization of Acyl-CoA Binding Protein Confers Autophagy-Dependent Organ Protection
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Project description:The Mycobacterium tuberculosis acyl-CoA carboxylases provide the building blocks for de novo fatty acid biosynthesis by fatty acid synthase (FAS) I and for the elongation of FAS I end-products by the FAS II complex to produce meromycolic acids. M. tuberculosis genome contains three biotin carboxylase subunits (AccA1-3) and 6 carboxyltransferase subunits (AccD1-6) of which AccD6 is located in a genetic locus that contains members of the FAS II complex. We found by microarray and quantitative real-time RT-PCR analysis that the transcripts of AccA3, AccD4, AccD5 and AccD6 are expressed at high levels during exponential growth phases of M. tuberculosis in vitro. Keywords: Time course, developmental stages
2006-10-07 | GSE5977 | GEO
Project description:Floodings already have a nearly 60% share in the worldwide damage to crops provoked by natural disasters. Climate change will cause plants to be even more frequently exposed to oxygen limiting conditions (hypoxia) in the near future due to heavy precipitation and concomitant waterlogging or flooding events in large areas of the world. Although the homeostatic regulation of adaptive responses to low oxygen stress in plants is well described, it remained unknown by which initial trigger the molecular response to low-oxygen stress is activated. Here, we show that a hypoxia-induced decline of the ATP level of the cell reduces LONG-CHAIN ACYL-COA SYNTHETASE (LACS) activity, which leads to a shift in the composition of the acyl-CoA pool. High oleoyl-CoA levels release the transcription factor RELATED TO APETALA 2.12 (RAP2.12) from its interaction partner ACYL-COA BINDING PROTEIN (ACBP) at the plasma membrane to induce low oxygen-specific gene expression. We show that different acyl-CoAs provoke unique molecular responses revealing a novel role as cellular signalling component also in plants. In terms of hypoxia signalling, dynamic acyl-CoA levels integrate the cellular energy status into the oxygen signalling cascade with ACBP and RAP2.12 being the central hub. The conserved nature of the ACBP:RAP2.12 module in crops and the novel mechanistic understanding of how low-oxygen stress responses are initiated by oleoyl-CoA in plants provide useful leads for enhancing future food security.
2018-04-30 | GSE97186 | GEO
Project description:G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl- CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with 5 th instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.
2022-05-04 | GSE201939 | GEO
Project description:Lipid mal-metabolism, particularly fatty acid oxidation (FAO) dysfunction, is a major driver of renal fibrosis. However, detailed regulatory mechanisms underlying this process remain unclear. In this study, we demonstrated that acyl-CoA thioesterase 12 (Acot12) is a key regulator of lipid metabolism in fibrotic kidneys. A significantly decreased level of ACOT12 was observed in a kidney sample of human patients with chronic kidney disease as well as in mouse kidney injury. Acot12 deficiency induces lipid accumulation and fibrosis in mice subjected to unilateral ureteral obstruction (UUO). Fenofibrate administration does not reduce renal fibrosis in Acot12-/- mice with UUO. Moreover, restoration of peroxisome proliferator-activated receptor (PPAR in Acot12-/- Ppar-/- kidneys with UUO exacerbated lipid accumulation and renal fibrosis, whereas restoration of Acot12 in Acot12-/- Ppar-/- kidneys with UUO significantly reduced lipid accumulation and renal fibrosis suggesting, mechanistically, Acot12 deficiency exacerbates renal fibrosis independently of PPAR. In Acot12-/- kidneys with UUO, a reduction in the selective autophagic degradation of peroxisomes and pexophagy with a decreased level of ACBD5 was observed. In conclusion, our study demonstrates the functional role and mechanistic details of Acot12 in the progression of renal fibrosis, provides a preclinical rationale for regulating Acot12 expression and presents a novel means of preventing renal fibrosis.
2025-03-12 | GSE261115 | GEO