Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Extracellular adenine released by the cardiac muscle cell disrupts pyrimidine biosynthesis in non-muscle cells to regulate tissue repair after heart injury

ABSTRACT: Extracellular adenine released by the cardiac muscle cell disrupts pyrimidine biosynthesis in non-muscle cells to regulate tissue repair after heart injury

PROVIDER: PRJNA767550 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR16126407_1.fastq.gz	Fastqsanger.gz
	SRR16126407_2.fastq.gz	Fastqsanger.gz
	SRR16126408_1.fastq.gz	Fastqsanger.gz
	SRR16126408_2.fastq.gz	Fastqsanger.gz
	SRR16126409_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 74

Similar Datasets

Extracellular adenine released by the cardiac muscle cell disrupts pyrimidine biosynthesis in non-muscle cells to regulate tissue repair after heart injury

Project description:Organ metabolism is spatio-temporally regulated at the cellular and tissue level to link metabolic pathways with key homeostatic processes, but little is known about the cellular regulation of metabolism during tissue repair after acute injury. In a murine model of ischemic cardiac injury, we demonstrate that the cardiac muscle cell regulates pyrimidine biosynthesis of non-muscle cells to affect cardiac repair. We demonstrate that the ectonucleotidase ENPP1 hydrolyzes extracellular ATP released after cardiac injury to form AMP, which then induces the cardiomyocyte to release adenine and specific ribonucleosides that disrupt pyrimidine biosynthesis, cause genotoxic stress and induce a p53 mediated cell death of non-myocyte cells such as fibroblasts, macrophages, endothelial and smooth muscle cells. As non-myocyte cells play a critical role in mediating heart repair, we demonstrate that rescue of pyrimidine biosynthesis by administration of uridine after cardiac injury or by genetic targeting of ENPP1/AMP pathway enhances repair and post infarct heart function. We establish a high through- put assay to screen a large library of small molecules to identify small molecule ENPP1 inhibitors and demonstrate that systemic administration of ENPP1 inhibitors following heart injury rescues pyrimidine biosynthesis in non-myocyte cells and augments tissue repair and function. We determine specific biochemical steps of pyrimidine biosynthesis that are disrupted and identify the critical pyrimidine metabolite orotidine as a serum biomarker for monitoring the metabolic control of tissue repair. These observations demonstrate that the cardiac muscle cell by releasing adenine regulates pyrimidine metabolism in non-muscle cells via paracrine mechanisms and provide insight into how inter-cellular regulation of pyrimidine biosynthesis can be targeted and monitored for augmenting tissue repair.

2021-11-03 | GSE185060 | GEO

Aging disrupts gene expression timing during muscle regeneration

Project description:Aging disrupts gene expression timing during muscle regeneration

| PRJNA747053 | ENA

Inhibition of pyrimidine biosynthesis targets protein translation in AML

Project description:Inhibition of pyrimidine biosynthesis targets protein translation in AML

| PRJNA752897 | ENA

Inhibition of pyrimidine biosynthesis targets protein translation in AML [Targeted_CRISPR_screen]

Project description:Inhibition of pyrimidine biosynthesis targets protein translation in AML [Targeted_CRISPR_screen]

| PRJNA752908 | ENA

Adenine effect on Enterohemorraghic E.coli

Project description:Previous experiments have shown that E. feacalis increases EHEC virulence by secreting adenine, this RNAseq aims to understand the molecular mechanism underlaying adenine role on EHEC

2024-05-01 | GSE244178 | GEO

Binge Alcohol Disrupts Skeletal Muscle Core Molecular Clock Independent of Glucocorticoids

Project description:Binge Alcohol Disrupts Skeletal Muscle Core Molecular Clock Independent of Glucocorticoids

| PRJNA761654 | ENA

Binge Alcohol Disrupts Skeletal Muscle Core Molecular Clock Independent of Glucocorticoids

Project description:Circadian rhythms are central to optimal physiological functioning and their interruption contributes to the development of several chronic diseases. Alcohol (EtOH) intoxication disrupts circadian rhythms within liver, brain, and intestines, but it is unknown whether alcohol also disrupts components of the core clock in skeletal muscle. Female C57BL/6Hsd mice were randomized to receive either saline (control) or alcohol (EtOH) (5g/kg) via intraperitoneal injection at the start of the dark cycle (ZT12), and gastrocnemius was collected every 4hr from Control and EtOH treated mice for the next 48hr following isoflurane anesthetization. In addition, metyrapone was administered prior to alcohol intoxication in separate mice to determine whether the alcohol-induced increase in serum corticosterone contributed to circadian gene regulation. Finally, synchronized C2C12 myotubes were treated with alcohol (100mM) to assess the influence of centrally or peripherally mediated effects of alcohol on the muscle clock. Alcohol significantly disrupted the mRNA expression of Bmal1, Per1/2, and Cry1/2 in addition to perturbing the clock-controlled genes, Myod1, Dbp, Tef, and Bhlhe40 (p<0.05). Alcohol increased serum corticosterone levels and glucocorticoid target genes, Redd1 and Klf15, in muscle. Metyrapone decreased serum corticosterone in EtOH mice but did not normalize the mRNA expression of Per1, Cry1 and Cry2 and Myod1 which were altered by EtOH. Alcohol did not alter core clock gene expression (Bmal, Per1/2, Cry1/2) at 4, 8, and 12hrs post treatment in synchronized C2C12 myotubes. Therefore, binge alcohol disrupted genes of the core molecular clock independently of elevated serum corticosterone.

2021-09-10 | GSE183665 | GEO

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_MN]

Project description:Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_MN]

| PRJNA752900 | ENA

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_I1DN]

Project description:Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_I1DN]

| PRJNA752905 | ENA

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_RUNX1]

Project description:Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_RUNX1]

| PRJNA752906 | ENA