Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of a high glucose induced oxidative stress and apoptosis model on primary rat cardiomyocytes

ABSTRACT: Diabetic hyperglycemia promotes reactive oxygen species (ROS) production to lead to oxidative stress and apoptosis responsible for progressive deterioration of the structure and function of organs. It has been indicated that factors and pathways regulating ROS production and the cellular redox state play a key role in the progression of diabetes and diabetes complications including cardiomyopathy. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of oxidative stress and apoptosis activity. In this study, we first established a high glucose induced oxidative stress and apoptosis model on primary rat cardiomyocytes. ROS formation and apoptosis activity were significantly increased at 24h/48h after high glucose stimulation. RNA sequencing analysis was applied to detect differentially expressed lncRNAs during cardiomyocytes oxidative stress and apoptosis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE109441 | GEO | 2019/01/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inhibition of 12/15-Lipoxygenase Protects Against β Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes

Project description:Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-lipoxygenase (12/15-LOX) is induced in β cells and macrophages during T1D and produces pro-inflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling suggested reduced promiscuity of ML351 compared to ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of pro-inflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced β-cell oxidative stress, and preservation of β-cell mass. In the non-obese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced β-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in the insulitis. Our data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of β-cell dysfunction and glycemic deterioration in models of T1D.

2017-10-29 | GSE101722 | GEO

Thioredoxin-1 promotes the restoration of alveolar bone in periodontitis with diabetes

Project description:Treatment of periodontitis in people with diabetes remains challenging. Diabetes-enhanced oxidative stress is a primary cause of aggravation of periodontitis. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1), an essential endogenous antioxidant protein, in the management of periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/β-catenin signal pathway. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/β-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.

2023-09-06 | GSE235930 | GEO

RNA-seq of a high glucose induced oxidative stress and apoptosis model on primary rat cardiomyocytes

Project description:RNA-seq of a high glucose induced oxidative stress and apoptosis model on primary rat cardiomyocytes

| PRJNA430889 | ENA

Molecular mechanism underlying increased ischemic damage in the ALDH2*2 genetic polymorphism using a human iPSC model system

Project description:We investigated the ALDH2*2 genetic polymorphism and its underlying mechanisms for the first time in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation confers elevated levels of reactive oxygen species (ROS) and toxic aldehydes such as 4HNE, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. ALDH2 exerts control of cell survival decisions via modulation of oxidative stress levels. This regulatory circuitry was found to be dysfunctional in the loss-of-function ALDH2*2 genotype, causing upregulation of apoptosis in cardiomyocytes following ischemic insult. These results reveal a novel function of the metabolic enzyme ALDH2 in modulation of cell survival decisions. Molecular mechanism of increased ischemic damage in cardiomyocytes of ALDH2*2 genotype.

2014-07-07 | E-GEOD-59100 | biostudies-arrayexpress

Effects of Medwakh Smoking on Oxidative Stress and Inflammation Among Youth in UAE using Liquid chromatography-mass spectrometry

Project description:Oxidative stress and inflammation are closely related, and inter-dependent pathophysiological processes. Oxidative stress plays a key role in the pathophysiology of several chronic inflammatory conditions that causes cellular alterations such as lipid damage, increase of cell permeability, apoptosis/cell death, alteration in growth factors, and signaling pathways.An imbalance between the production of reactive oxygen species (ROS) and their neutralization by the antioxidant system results in the onset of oxidative stress which subsequently leads to the release of chronic inflammatory mediators such as pro-inflammatory cytokines, which causes damages to DNA, proteins, and lipids.LC-MSMS is widely used for non-targeted and non-invasive metabolomics of biological samples including saliva in a variety of conditions such as inflammatory conditions, cancers, diabetes, etc. However, to the best of our knowledge, there are currently no metabolomics-based studies identifying salivary biomarkers associated with inflammation and oxidative stress utilizing HPLC-ESI-QTOF-MS. Therefore, in this study, we aim to discover the biochemical and physiological changes induced by medwak smoking and explore the metabolomics profile of medwak smokers with a focus on the markers of oxidative stress and inflammation in comparison to nonsmokers.

2022-06-20 | ST002211 | MetabolomicsWorkbench

Modulation of NOX2 causes Obesity- Mediated Atrial Fibrillation

Project description:Obesity is linked to an increased risk of atrial fibrillation (AF) via increased oxidative stress. While NADPH oxidase II (NOX2), a major source of oxidative stress and reactive oxygen species (ROS) in the heart predisposes to AF, the underlying mechanisms remain unclear. Here, we studied NOX2-mediated ROS production in obesity-mediated AF using Nox2-knock-out (KO) mice and mature human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). Diet-induced obesity (DIO) mice and hiPSC-aCMs treated with palmitic acid (PA) were infused with a NOX blocker (apocynin) and a NOX2-specific inhibitor, respectively. We showed that NOX2 inhibition normalized atrial action potential duration and abrogated obesity-mediated ion channel remodeling with reduced AF burden. Unbiased transcriptomics analysis revealed that NOX2 mediates atrial remodeling in obesity-mediated AF in DIO mice, PA-treated hiPSC-aCMs, and human atrial tissue from obese individuals by upregulation of paired-like homeodomain transcription factor 2 (PITX2). Furthermore, hiPSC-aCMs treated with hydrogen peroxide, a NOX2 surrogate, displayed increased PITX2 expression, establishing a mechanistic link between increased NOX2-mediated ROS production and modulation of PITX2. Our findings offer insights into possible mechanisms through which obesity triggers AF and support NOX2 inhibition as a potential novel prophylactic or adjunctive therapy for patients with obesity-mediated AF.

2024-10-09 | GSE271748 | GEO

Site-specific Identification and Quantification of Protein Glutathionylation under Ischemic Stress

Project description:Ischemia or ischemic reperfusion is well-known for its contribution to heart diseases. During ischemia and reperfusion, a flux of nutrients and oxygen to cardiomyocytes is altered, which causes a burst of ROS from mitochondria and other enzymes. Elevated levels of ROS can cause oxidative modifications of cardiac proteins, such as protein glutathionylation. Despite previous extensive studies, proteomic identification of glutathionylated proteins in cardiomyocytes under altered levels of nutrients and oxygen has been relatively limited. We have applied our clickable glutathione approach to HL-1 cardiomyocyte cell line under metabolic alterations of glucose, oxygen, and fatty acids to detect and identify proteins undergoing glutathionylation.

2021-08-13 | PXD024766 | Pride

Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.

Project description:Paracetamol (acetaminophen, APAP) overdose severely damages mitochondria and triggers several apoptotic processes in hepatocytes, but the final outcome is fulminant necrotic cell death, resulting in acute liver failure and mortality. Here, we studied this switch of cell death modes and demonstrate a non-canonical role of the apoptosis-regulating BCL-2 homolog BIM/Bcl2l11 in promoting necrosis by regulating cellular bioenergetics. BIM deficiency enhanced total ATP production and shifted the bioenergetic profile towards glycolysis, resulting in persistent protection from APAP-induced liver injury. Modulation of glucose levels and deletion of mitofusins confirmed that severe APAP toxicity occurs only in cells dependent on oxidative phosphorylation. Glycolytic hepatocytes maintained elevated ATP levels and reduced ROS, which enabled lysosomal recycling of damaged mitochondria by mitophagy. The present study highlights how metabolism and bioenergetics affect drug-induced liver toxicity, and identifies BIM as important regulator of glycolysis, mitochondrial respiration, and oxidative stress signaling.

2023-09-08 | GSE242368 | GEO

Human Pancreatic Beta Cell lncRNAs Control Cell-Specific Regulatory Networks

Project description:Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.

| EGAS00001002865 | EGA

Gene expression from pericytes and endothelial cells

Project description:Aims: Vascular wall resident stem cells (SCs) hold great promise for cardiovascular regenerative therapy. This study evaluated the impact of oxidative stress on the viability and functionality of saphenous vein'derived pericytes (SVPs), SVPs'deriv ed cells and terminally differentiated vascular cells. We also investigated the molecular mechanisms underlying the SVP resistance to oxidative stress. Results: SVPs exhibit a significantly higher resistance to oxidative stress resulting in reduced apoptosis upon exposure to hydrogen peroxide in comparison to endothelial cells (ECs). This was attributed to upregulation of genes encoding for anti'oxidant enzymes, especially superoxide dismutases (SODs) and catalase. Pharmacological inhibition of SODs increased ROS levels in SVPs and impaired their survival. Furthermore, we confirm that, when exposed to differentiation stimuli, SVPs are able to generate mesodermic lineages. Interestingly, differentiation of SVPs resulted in SOD down'regulation and increased apoptosis upon exposure to hydrogen peroxide. Oxidative stress caused an incremental increase on SVPs migration, whilst being inhibitory for the ECs. Additionally, oxidative stress did not impair SVPs capacity to promote angiogenesis in vitro. Innovations: This study for the first time demonstrates that SCs resident in veins of cardiovascular patients are endowed with enhanced detoxifier and antioxidant system. Conclusions: SVPs expanded from vein remnants of coronary artery bypass graft surgery express antioxidant defense mechanisms which allow them resist to high levels of ROS. These properties highlight the potential of SVPs in cardiovascular regenerative medicine. 2 groups 3 replicates

2014-01-01 | E-GEOD-50758 | biostudies-arrayexpress

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