Circ_0008146 exacerbates ferroptosis via regulating miR-342-5p/ACSL4 axis after cerebral ischemia-reperfusion in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1069739 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27744379.fastq.gz | Fastqsanger.gz | |||
| SRR27744380.fastq.gz | Fastqsanger.gz | |||
| SRR27744381.fastq.gz | Fastqsanger.gz | |||
| SRR27744382.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Background: Characterized by high incidence, mutilation, and death rate, acute ischemic stroke (AIS) has threatened people’s health seriously. Therefore, there is an urge need for early diagnosis and effective treatment of AIS. The purpose of this study was to clarify the regulatory role and potential molecular mechanism of miR-342-5p and circRNA_0008146 in AIS. Materials and Methods: Small RNA sequencing analysis was performed to screen differentially expressed miRNAs between the AIS and control group. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. The circRNA_0008146 and miRNA expression levels were detected by quantitative real-time PCR. Assay kits were used to determine Fe2+ levels and assess a battery of oxidative stress indicators, including ROS, MDA, LPO, SOD, and GSH/GSSG. The content of ACSL4 was measured by Western blot. The neurobehavioral manifestation was evaluated using the modified Neurological Severity (mNSS) Score, rotarod test, and corner test. TTC staining was employed to detect cerebral infarction volume. Nissl staining was adapted to detect histological change and neuronal damage. Results: RNA sequencing analysis revealed miR-342-5p was significantly downregulated in the plasma of AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic-reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. CircRNA_0008146 acted as a sponge of miR-342-5p, and overexpression of circRNA_0008146 increased brain damage in stroke mice. CircRNA_0008146 contributed to ferroptosis in cerebral infraction via sponging miR-342-5p to regulate ACSL4. Conclusion: CircRNA_0008146/miR-342-5p/ACSL4 axis regulate ferroptosis after cerebral ischemia-reperfusion, which may be a potential therapeutic target for ischemic stroke.
2024-08-08 | GSE254322 | GEO
Project description:Analysis of acute kidney injury (AKI) with knockdown of ACSL4. Results provide insight into the role of ACSL4 in the regulation of ferroptosis.
2022-02-23 | GSE181842 | GEO
Project description:ACSL4 effect on renal ischemia-reperfusion (I/R) injury
| PRJNA753588 | ENA
Project description:The myokine irisin is involved in the regulation of a variety of physiological conditions, metabolism, and survival. We and others have demonstrated that recombinant irisin contributes critically to modulation of insulin resistance and cardiac function. However, the molecular mechanisms by which irisin exerts its physiological effects on cardiac function and insulin sensitivity remain unclear. We utilized the CRISPR/Cas9 genome editing system to delete irisin. Irisin deficiency did not result in abnormalities in development, growth, or cardiac function; however, gene expression profiling showed that several key signaling pathways related to growth, insulin signaling, and integrin signaling were coordinately downregulated. However, loss of irisin resulted in more severe insulin resistance and metabolic derangement when mice were exposed to a high fat diet, which was associated with profound cardiac dysfunction and hypertrophic remodeling. In addition, the loss of irisin also exacerbated myocardial ischemia-reperfusion injury, as indicated by a reduction of post-ischemic ventricular function and an increase in infarct size. Taken together, our results indicate that loss of irisin exacerbates insulin resistance and cardiac depression in response to high fat diet and promotes myocardial ischemia-reperfusion injury. This evidence suggests a role for irisin in modulating insulin resistance, cardiac function and ischemic injury.
2023-11-08 | GSE231597 | GEO
Project description:Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation (LT); however, the potential mechanism remains unclear. Here, we demonstrated older livers exhibit a higher degree of ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuated older HIRI. Mass spectrometry revealed fat mass and obesity-associated gene (FTO) was downregulated in older livers, especially during HIRI. Overexpressing FTO ameliorated older HIRI by inhibiting ferroptosis. Mechanistically, ACSL4 and TFRC, two key positive contributors of ferroptosis, were targets of FTO. The mitigating effect of FTO on older HIRI required the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrated nicotinamide mononucleotide (NMN) could upregulate FTO demethylase activity to suppress ferroptosis and attenuate older HIRI. Collectively, these findings revealed an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO in order to improve graft function after older donor LT.
2024-04-12 | PXD051387 |
Project description:Klebsiella pneumoniae 342 isolate:342 Genome sequencing
| PRJNA1280976 | ENA
Project description:In order to investigate the differentially expressed genes in Acsl4 knockout after TAC (Transverse aortic constriction) or sham surgery. The experiment was divided to four groups including sham-operated Acsl4 flox/flox mice (FS), sham-operated Acsl4 knockout mice (KS), TAC-operated Acsl4 flox/flox mice (FT), TAC-operated Acsl4 knockout mice (KT) n=3 mice/group. The heart tissue was isolated after 21 days after performing TAC or sham surgery.
2024-08-26 | E-MTAB-14383 | biostudies-arrayexpress
Project description:ACSL4 expression appears to be inversely associated with steroid hormone and growth factor receptor expression in breast cancer and positively correlated with an aggressive breast cancer phenotype. Neither MCF-7 nor SKBr3 cells normally express ACSL4, and when manipulated to do so, develop basal-like characteristics, including increased proliferation, migration and anchorage independent growth. We used an Affymetrix array platform to assess changes in individual gene expression as a function of conditional and stable expression of ACSL4 in MCF-7 and SKBr3 cells. In experiment 1, MCF-7 Tet-ON cells were transfected with ACSL4 cDNA and induced to express ACSL4 by addition of 1ug/ml of doxycycline (A) or vehicle (C) for 72 hours. Three controls (C) and three doxycycline-induced (A) samples were evaluated for gene expression. In experiment 2, MCF-7 cells were stably transfected with either an empty vector (C) or Lenti-ORF-ACSL4 (A). In experiment 3, SKBr3 cells were stably transfected with either an empty vector (C) or Lenti-ORF-ACSL4 (A).
2012-09-19 | E-GEOD-40968 | biostudies-arrayexpress
Project description:Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.
| S-EPMC8866433 | biostudies-literature
Project description:Metabolic reprogramming is often observed in sepsis-associated encephalopathy (SAE). However, little is known about the aberrant metabolic genes involved in mitochondrial damage, neuroinflammation, and lipid accumulation in microglial cells. Here, we show that hexokinase 2 (HK2) is upregulated and is strongly associated with the inflammatory response and lipid metabolism in lipopolysaccharide-induced BV2 cells. Genetic silencing or pharmacological inhibition of HK2 attenuates mitochondrial damage in vitro. Downregulation of HK2 lowered the NOD-like receptor signaling family pyrin domain containing three activations, both in BV2 cells and in the hippocampus of cecal ligation and puncture-induced male septic mice. Moreover, the inhibition of HK2 promoted lipid droplet reduction and activated mammalian target of rapamycin-mediated autophagy. Mechanistically, HK2 knockdown in microglial cells reduced the ISGylation of Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4) during lipid metabolism by interferon-stimulated gene 15 (ISG15). Notably, ISG15 effectively down-regulated the expression of ACSL4 in vitro. Our findings provide new mechanistic insights of HK2 in microglial cells through regulation of ACSL4 ISGylation, suggesting a promising therapeutic strategy for treating SAE by targeting HK2.
2025-04-30 | GSE280721 | GEO