Gene expression in Tetrahydrocurcumin-treated HUVEC cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE303488 | GEO | 2026/02/24
REPOSITORIES: GEO
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Project description:Chen2006 - Nitric Oxide Release from
Endothelial Cells
This model is described in the article:
Theoretical analysis of
biochemical pathways of nitric oxide release from vascular
endothelial cells.
Chen K, Popel AS.
Free Radic. Biol. Med. 2006 Aug; 41(4):
668-680
Abstract:
Vascular endothelium expressing endothelial nitric oxide
synthase (eNOS) produces nitric oxide (NO), which has a number
of important physiological functions in the microvasculature.
The rate of NO production by the endothelium is a critical
determinant of NO distribution in the vascular wall. We have
analyzed the biochemical pathways of NO synthesis and
formulated a model to estimate NO production by the
microvascular endothelium under physiological conditions. The
model quantifies the NO produced by eNOS based on the kinetics
of NO synthesis and the availability of eNOS and its
intracellular substrates. The predicted NO production from
microvessels was in the range of 0.005-0.1 microM/s. This range
of predicted values is in agreement with some experimental
values but is much lower than other rates previously measured
or estimated from experimental data with the help of
mathematical modeling. Paradoxical discrepancies between the
model predictions and previously reported results based on
experimental measurements of NO concentration in the vicinity
of the arteriolar wall suggest that NO can also be released
through eNOS-independent mechanisms, such as catalysis by
neuronal NOS (nNOS). We also used our model to test the
sensitivity of NO production to substrate availability, eNOS
concentration, and potential rate-limiting factors. The results
indicated that the predicted low level of NO production can be
attributed primarily to a low expression of eNOS in the
microvascular endothelial cells.
This model is hosted on
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BIOMD0000000676.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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2024-09-02 | BIOMD0000000676 | BioModels
Project description:The dysfunction of endothelial nitric oxide synthase may be involved in development of atherosclerosis; however, the underlying molecular and cellular mechanisms of atherosclerosis are poorly understood. Here, we investigated gene expressionsin relation to atherosclerosis using endothelial nitric oxide synthase (eNOS)-deficient mice.
2018-12-15 | GSE123855 | GEO
Project description:Recent genome-wide association studies have identified PHACTR1 as a critical risk gene associated with polyvascular diseases. However, it remains elusive how PHACTR1 is involved in endothelial dysfunction. Here, we show that PHACTR1 triggers endothelial inflammation by activating NF-κB and disrupts Nitric oxide production by inhibiting Akt/eNOS activation to induce endothelial diastolic disorder. Whereas, Atorvastatin particularly plays an inhibitory effect on PHACTR1 gene expression in a dose-dependent manner among PHACTR family in endothelial cells. PHACTR1 may interact with PP1 with coupling with heat shock protein 8 (HSPA8) to dephosphorylate Akt or eNOS.
2022-08-16 | PXD034213 | Pride
Project description:Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of L-arginine and molecular oxygen into L-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist stimulated NO synthesis and decreased phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells.
2018-10-24 | PXD002598 | Pride
Project description:Soon after release from stemness, a relevant portion of mouse embryonic stem cells (mES), kept in naïve state by MEK inhibitor, GSK3 inhibitor and LIF (2i/L), expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes nitric oxide (NO). In this condition, an eNOS/NO-positive subpopulation (ESNO+) has been recognized by 4-amino-5-methylamino-2′,7′-difluorescein (DAF) fluorescence. Sorted ESNO+ cells expressed high levels of mesendodermal markers and efficiently generated cardiovascular precursors compared to eNOS/NO-negative cells (ESNO-). Mechanistically, the endogenous NO production deter- mined a rapid S-nitrosylation of Hdac2, a post-translational modification that compromised Hdac2 association with the transcription repression factor Zeb1. This condition destabilized Zeb1/chromatin interaction with genomic loci encoding for mesendodermal genes. Remarkably, Zeb1 or Hdac2 targeting activated an unscheduled transcription of mesendodermal lineage-associated genes in naïve mES revealing the Hdac2-Zeb1 pathway important for stemness maintenance in 2i/L. In contrast, eNOS targeting significantly reduced the endogenous NO production preventing the activation of mesendodermal gene transcription.
2018-10-31 | GSE104646 | GEO
Project description:Soon after release from stemness, a relevant portion of mouse embryonic stem cells (mES), kept in naïve state by MEK inhibitor, GSK3 inhibitor and LIF (2i/L), expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes nitric oxide (NO). In this condition, an eNOS/NO-positive subpopulation (ESNO+) has been recognized by 4-amino-5-methylamino-2′,7′-difluorescein (DAF) fluorescence. Sorted ESNO+ cells expressed high levels of mesendodermal markers and efficiently generated cardiovascular precursors compared to eNOS/NO-negative cells (ESNO-). Mechanistically, the endogenous NO production deter- mined a rapid S-nitrosylation of Hdac2, a post-translational modification that compromised Hdac2 association with the transcription repression factor Zeb1. This condition destabilized Zeb1/chromatin interaction with genomic loci encoding for mesendodermal genes. Remarkably, Zeb1 or Hdac2 targeting activated an unscheduled transcription of mesendodermal lineage-associated genes in naïve mES revealing the Hdac2-Zeb1 pathway important for stemness maintenance in 2i/L. In contrast, eNOS targeting significantly reduced the endogenous NO production preventing the activation of mesendodermal gene transcription.
2018-10-31 | GSE104647 | GEO
Project description:Lupus nephritis (LN) is characterized by renal endothelial dysfunction, which contributes to progressive kidney injury. Endothelial nitric oxide synthase (eNOS) plays a modulating role in LN, as genetic ablation of the eNOS enzyme worsens disease. Serum from patients with active LN induces uncoupling of eNOS homodimers, leading to superoxide (SO) rather than nitric oxide (NO) production by eNOS. This uncoupling is reversed with L-sepiapterin (L-Sep). This study was designed to further examine changes in gene expression in glomerular endothelial cells induced by LN serum and whether treatment with L-Sep can ameliorate these changes. Methods Primary human renal glomerular endothelial cells (HRGECs) were cultured with serum from non-lupus controls (HC), LN patients during remission (LN rem), or LN patients during flare (LN flare) with and without L-Sep. Bulk RNA sequencing was performed on RNA isolated from cultured cells. Differential gene expression was determined, and pathway and gene enrichment analyses were performed on differentially expressed genes. Results L-Sep treatment induced differential gene expression after culture in HRGECs cultured with LN flare serum. Addition of L-Sep induced genes involved in promoting endothelial function and enriched for pathways of NO biosynthetic and metabolic processes, fatty acid and lipid biosynthesis, neurotransmitter biosynthesis, reactive oxygen biosynthesis, vascular endothelial growth factor production, and regulation of smooth muscle contraction. Conclusions These results indicate that glomerular endothelial cells can mount an active inflammatory response in an LN serum environment. More importantly, L-Sep modulates gene expression in a fashion consistent with reduction of oxidative stress and increased NO production. These findings provide the rationale to target endothelial dysfunction to modulate LN with L-Sep as a therapeutic.
2025-06-18 | GSE296560 | GEO
Project description:Sash1 acts as a scaffold in TLR4 signaling. We generated Sash1-/- mice, which die in the perinatal period due to respiratory distress. Constitutive or endothelial-restricted Sash1 loss leads to a reduction of surfactant-associated protein synthesis. We show that Sash1 interacts with β-arrestin 1 downstream of the TLR4 pathway to activate Akt and eNOS in microvascular endothelial cells. Generation of nitric oxide downstream of Sash1 in endothelial cells activated cGMP in adjacent alveolar type 2 cells to induce transcription of surfactant genes. Thus we identify a critical cell nonautonomous function for Sash1 in embryonic development in which endothelial Sash1 affects alveolar type 2 cells and promotes pulmonary surfactant production through nitric oxide signaling. Lack of pulmonary surfactant is a major cause of respiratory distress and mortality in preterm infants, and these findings identify the endothelium as a potential target for therapy.
2019-05-01 | GSE123889 | GEO
Project description:Regulation of endothelial cell (EC) lipid content is crucial for cell and organ function. During obesity, ECs become lipid laden leading to lipotoxicity and endothelial dysfunction which further contribute to metabolic syndrome progression. Here, we demonstrate a novel pathway by which the endothelium, via eNOS-dependent nitrosation, inhibits excess lipid accumulation during hyperlipidemic conditions in obesity. In the vasculature, nitric oxide has been reported as a potent vasodilator. However, we highlight a new role for nitric oxide as a modulator of serum lipids. We show this occurs as a result of the downregulation of Cav1, a potent negative regulator of endothelial nitric oxide synthase, increasing EC endogenous nitric oxide synthesis. Using EC-specific Cav1 knockout mice, we are able to increase nitric oxide in vivo. This increased nitric oxide leads to nitrosation of cysteines 3 and 466 on the cytoplasmic tails of CD36, a fatty acid translocase, disrupting palmitoylation of these residues and subsequently inhibiting trafficking of CD36 to the plasma membrane. Together, this work suggests that CD36 nitrosation occurs as a protective mechanism to prevent lipotoxicity and EC dysfunction during the progression of metabolic syndrome.
2024-12-31 | GSE260897 | GEO
Project description:The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identified an enhancer-associated lncRNA that enhances eNOS expression” (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrated that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Deletion of LEENE enhancer locus decreases the LEEN-eNOS proximal association and eNOS mRNA level. Inhibition of LEENE using locked nucleic acids (LNA) decreases eNOS expression and monocyte adhesion to ECs, whereas overexpression of LEENE increases eNOS expression and eNOS-derived NO in ECs. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.
2017-10-18 | GSE103649 | GEO