Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chronic alcohol metabolism results in DNA repair infidelity and cell-cycle-induced senescence in neurons

ABSTRACT: Chronic alcohol metabolism results in DNA repair infidelity and cell-cycle-induced senescence in neurons

PROVIDER: PRJNA834950 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19077300.fastq.gz	Fastqsanger.gz
	SRR19077301.fastq.gz	Fastqsanger.gz
	SRR19077302.fastq.gz	Fastqsanger.gz
	SRR19077291.fastq.gz	Fastqsanger.gz
	SRR19077292.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Chronic alcohol metabolism results in DNA repair infidelity and cell-cycle-induced senescence in neurons

Project description:Chronic and excessive binge-like drinking is a risk factor to pathological cognitive decline and dementia, but the mechanism underlying the prolonged and lasting effect of alcohol even in abstainers remains elusive. This study investigates how ethyl alcohol directly results in metabolic reprograming and persistent physiological changes in brain cells that underlies such effect.

2023-02-22 | GSE202183 | GEO

Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons.

Project description:Chronic binge-like drinking is a risk factor for age-related dementia, however, the lasting and irreversible effect of alcohol on the brain remains elusive. Transcriptomic changes in brain cortices revealed pro-ageing hallmarks upon chronic ethanol exposure and these changes predominantly occur in neurons. The changes are attributed to a prioritized ethyl alcohol oxidation in these cells via the NADPH-dependent cytochrome pathway. This hijacks the folate metabolism of the 1-carbon network which supports the pathway choice of DNA repair via the non-cell cycle-dependent mismatch repair networks. The lost-in-function of such results in the de-inactivation of the less preferred cell cycle-dependent homologous recombination (HR) repair, forcing these post-mitotic cells to re-engage in a cell cycle-like process. However, mature neurons are post-mitotic. Therefore, instead of successfully completing a full round of cell cycle which is necessary for the completion of HR-mediated repair; these cells are arrested at checkpoints. The resulting persistence of repair intermediates induces and promotes the nuclear accumulation of p21 and cyclin B-a trigger for permanent cell cycle exits and irreversible senescence response. Supplementation of bioactive 5-methyl tetrahydrofolate simultaneously at times with ethyl alcohol exposure supports the fidelity of the 1-carbon network and hence the activity of the mismatch repair. This prevents aberrant and irreversible cell cycle re-entry and senescence events of neurons. Together, our findings offer a direct connection between binge-drinking behaviour and its irreversible impact on the brain, which makes it a potential risk factor for dementia.

| S-EPMC9924945 | biostudies-literature

Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution

Project description:Background & Aims: Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH. Methods: We performed RNA sequencing and bioinformatics analysis of transjugular liver biopsies (n=65) from AH patients participating in the ISAIAH clinical trial. We also carried out multiomic analysis of an in vitro hepatocyte model of AH. We also performed additional bioinformatics reanalysis of existing AH transcriptomic datasets. Results: Senescence markers and pathways are increasingly expressed in hepatocytes as ArLD progresses towards AH. We find dysregulation of senescence, inflammation and hepatocyte function is reversed at transcriptomic level following AH resolution. We identify dysregulation of two senescence-associated protein complexes, cytochrome c oxidase and the proteasome, which may act as senescence-induction mechanisms. Our in vitro model reveals senescence induction is a direct effect of ethanol on hepatocytes. Conclusions: Our results show a central role for senescence in AH and suggest senolytics as potential therapeutics in early ALD to limit AH severity.

2025-08-25 | PXD053109 | Pride

Reduced Abd-B Hox function during kidney development results in lineage infidelity

Project description:Reduced Abd-B Hox function during kidney development results in lineage infidelity

| PRJNA430800 | ENA

Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution I

Project description:Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH.

2025-03-28 | GSE269566 | GEO

Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution II

2025-03-28 | GSE270042 | GEO

Reduced Abd-B Hox function during kidney development results in lineage infidelity

Project description:In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the uretreric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments.

2018-01-20 | GSE109404 | GEO

Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy

Project description:Editing of mischarged tRNAs by cytoplasmic aminoacyl-tRNA synthetases (aaRSs) is of high significance for protein homeostasis, whose impairment causes neurodegeneration. However, whether mitochondrial translation needs fidelity and the significance of proofreading (editing) by mitochondrial aaRSs are long-term mysteries. Here, we showed that NIH-3T3 cell line critically depend on the editing of mitochondrial threonyl-tRNA synthetase (Tars2) editing, the disruption of which accumulated Ser-tRNAThr and generated a large abundance of Thr-to-Ser misincorporated peptides. Such infidelity impaired mitochondrial translation and oxidative phosphorylation, causing oxidative stress and cell cycle arrest at G0/G1 phase. ROS removal by N-acetylcysteine relieved abnormal cell proliferation.

2023-08-25 | GSE232410 | GEO

Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution

Project description:Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution

| PRJNA1124900 | ENA

Cancer immune control needs senescence induction by Stat1 dependent cell cycle regulator pathways in tumours

Project description:Immune checkpoint bloackade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a) in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.

| EGAS00001004151 | EGA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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