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Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop

ABSTRACT: Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop

PROVIDER: PRJNA1109283 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28962368_1.fastq.gz	Fastqsanger.gz
	SRR28962368_2.fastq.gz	Fastqsanger.gz
	SRR28962369_1.fastq.gz	Fastqsanger.gz
	SRR28962369_2.fastq.gz	Fastqsanger.gz

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Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop

Project description:Astrocytic metabolic reprogramming is an adaptation of metabolic patterns to meet increased energy demands, although the role after spinal cord injury (SCI) remains unclear. Analysis of single-cell RNA sequencing (scRNA-seq) data identified an increase in astrocytic glycolysis, while PFKFB3, a key regulator of glycolytic flux, was significantly upregulated following SCI. Loss of PFKFB3 in astrocytes prohibited neuronal energy supply and enhanced neuronal ferroptosis in vitro and inhibited astrogliosis, expanded neuroinflammation, exacerbated neuronal loss, and hindered functional recovery in vivo after SCI. Mechanistically, deubiquitinase UCHL1 plays a crucial role in stabilizing and enhancing PFKFB3 expression by cleaving K48-linked ubiquitin chains. Genetic deletion of Uchl1 inhibited locomotor recovery after SCI by suppression of PFKFB3-induced glycolytic reprogramming in astrocytes. Furthermore, the UCHL1/PFKFB3 axis increased lactate production, leading to enhanced histone lactylation and subsequent transcription of Uchl1 and several genes related to glycolysis, suggesting a glycolysis/H4K8la/UCHL1 positive feedback loop. These findings help to clarify the role of the UCHL1/PFKFB3/H4K8la loop in modulation of astrocytic metabolic reprogramming and reveal a potential target for treatment of SCI.

2025-02-21 | GSE266984 | GEO

Genes regulated by UCHL1 in ovarian cancer cells

Project description:UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1

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Genes regulated by UCHL1 in ovarian cancer cells

Project description:UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1 UCHL1 was knocked down in A2780 (A2780-shUCHL1). A2780-shUCHL1 and A2780-control were cultured in RPMI and total RNA was extracted and hybridizated on Affymetrix.GeneChip.HG-U133_Plus_2

2013-01-30 | E-GEOD-43884 | biostudies-arrayexpress

Gene expression data of PFKFB3 KD in SMMC7721 cell line

Project description:Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key molecule of glucose metabolism in cytoplasm, was found in various tumors. Emerging evidence suggested that PFKFB3 also located in nucleus and shown regulatory functions other than glycolysis. In this study, we found that PFKFB3 expression is associated with hepatocellular carcinoma (HCC) growth and mainly located in the nucleus of tumor cells. PFKFB3 overexpression was associated with large tumor size, and poor survival of patients with HCC. Knockdown of PFKFB3 inhibited HCC growth, not only by reducing glucose consuming but also damaging DNA repair function leading to G2/M phase arrest and apoptosis. Therefore, we performed a cDNA microarray in PFKFB3 knockdown SMMC7721 cells.

2018-03-01 | GSE106603 | GEO

Effect of PFKFB3 overexpression on A549 in VSV infection.

Project description:To investigate the function PFKFB3 in RNA virus infection, we established PFKFB3 overexpressed A549 cell lines and infected cells with VSV.

2025-08-01 | GSE210288 | GEO

Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is associated with shelterin complex at interstitial telomeric sites

Project description:Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells. It is a multifunctional protein involved in deubiquitination, ubiquitination, and ubiquitin homeostasis. UCHL1 has been associated with various diseases, including many cancers, but its specific roles are disputed and still generally undetermined. Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and TERF2IP, also a component of the shelterin complex, were bound to the nuclear scaffold. UCHL1 may play a role in regulating gene expression by affecting the stabilization of the shelterin proteins or influencing nuclear targeting. As several shelterin proteins (TRF1, TRF2, POT1 and TERF2IP) are ubiquitinated, UCHL1 may have a role in regulating the stability of these proteins. UCHL1 may also regulate the nuclear location of shelterin-associated genomic regions.

2018-02-23 | GSE97111 | GEO

PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells

Project description:We hypothesized that PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells (PMVECs) and found that PFKFB3 knockout cells survive better than wild type cells in fructose-rich media, more so under hypoxia. Our findings indicate that PFKFB3 is a molecular switch that controls glucose versus fructose utilization in glycolysis and help to better understand lung endothelial cell metabolism during respiratory failure.

2023-08-01 | GSE230660 | GEO

Differential gene expression in UCHL1 silenced ovarian cancer cells

Project description:We report dysregulated genes upon silencing UCHL1 in high-grade serous ovarian cancer cell line, Kuramochi.

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PFKFB3 activates CAD to enhance de novo pyrimidine synthesis for cell growth

Project description:Aerobic glycolysis, which is also termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. To date, no studies have explored interrelationships between glycolysis and other metabolic pathways. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three steps of de novo pyrimidine synthesis. PFKFB3 inactivation reduced de novo pyrimidine synthesis, RNA and DNA production, and the growth of cancer and proliferative cells. Thus, the glycolytic activator PFKFB3 bridges glycolysis with pyrimidine synthesis, unites both glucose metabolism and nucleic acid metabolism, and contributes to cell proliferation under both physiological and pathological conditions.

2025-06-16 | PXD048755 | Pride

UCHL1 Maintains Microenvironmental Homeostasis of Male Germline Stem Cells by Antagonizing HSPA8

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2026-07-01 | GSE237083 | GEO

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