scholarly journals Oxidative stress inactivates VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine nitration

2004 ◽  
Vol 118 (1) ◽  
pp. 243-252 ◽  
Author(s):  
Azza B. El-Remessy ◽  
Manuela Bartoli ◽  
Danial H. Platt ◽  
David Fulton ◽  
Ruth B. Caldwell
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Tyrosine Nitration ◽  
Retinal Endothelial Cells ◽  
Survival Signaling

scholarly journals Oxidative stress inactivates VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine nitration

2016 ◽  
Vol 129 (16) ◽  
pp. 3203-3203 ◽  
Author(s):  
Azza B. El-Remessy ◽  
Manuela Bartoli ◽  
Danial H. Platt ◽  
David Fulton ◽  
Ruth B. Caldwell
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Tyrosine Nitration ◽  
Retinal Endothelial Cells ◽  
Survival Signaling

scholarly journals CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 744-754 ◽  
Author(s):  
Yixin Tang ◽  
Elizabeth A. Scheef ◽  
Shoujian Wang ◽  
Christine M. Sorenson ◽  
Craig B. Marcus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Endothelial Cells ◽  
Retinopathy Of Prematurity ◽  
Cellular Responses ◽  
Retinal Endothelial Cells ◽  
Capillary Morphogenesis ◽  
Ischemic Retinopathy ◽  
Intracellular Oxidative Stress

Abstract Reactive species derived from cell oxygenation processes play an important role in vascular homeostasis and the pathogenesis of many diseases including retinopathy of prematurity. We show that CYP1B1-deficient (CYP1B1−/−) mice fail to elicit a neovascular response during oxygen-induced ischemic retinopathy. In addition, the retinal endothelial cells (ECs) prepared from CYP1B1−/− mice are less adherent, less migratory, and fail to undergo capillary morphogenesis. These aberrant cellular responses were completely reversed when oxygen levels were lowered or an antioxidant added. CYP1B1−/− ECs exhibited increased oxidative stress and expressed increased amounts of the antiangiogenic factor thrombospondin-2 (TSP2). Increased lipid peroxidation and TSP2 were both observed in retinas from CYP1B1−/− mice and were reversed by administration of an antioxidant. Reexpression of CYP1B1 in CYP1B1−/− ECs resulted in down-regulation of TSP2 expression and restoration of capillary morphogenesis. A TSP2 knockdown in CYP1B1−/− ECs also restored capillary morphogenesis. Thus, CYP1B1 metabolizes cell products that modulate intracellular oxidative stress, which enhances production of TSP2, an inhibitor of EC migration and capillary morphogenesis. Evidence is presented that similar changes occur in retinal endothelium in vivo to limit neovascularization.

Reactive oxygen species downregulate glucose transport system in retinal endothelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. C927-C936 ◽  
Author(s):  
Rosa Fernandes ◽  
Ken-ichi Hosoya ◽  
Paulo Pereira
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Plasma Membrane ◽  
Endothelial Cell ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Cell Damage ◽  
Proteasome Inhibition ◽  
Glucose Transporter 1 ◽  
Retinal Endothelial Cells

Retinal endothelial cells are believed to play an important role in the pathogenesis of diabetic retinopathy. In previous studies, we and others demonstrated that glucose transporter 1 (GLUT1) is downregulated in response to hyperglycemia. Increased oxidative stress is likely to be the event whereby hyperglycemia is transduced into endothelial cell damage. However, the effects of sustained oxidative stress on GLUT1 regulation are not clearly established. The objective of this study is to evaluate the effect of increased oxidative stress on glucose transport and on GLUT1 subcellular distribution in a retinal endothelial cell line and to elucidate the signaling pathways associated with such regulation. Conditionally immortalized rat retinal endothelial cells (TR-iBRB) were incubated with glucose oxidase, which increases the intracellular hydrogen peroxide levels, and GLUT1 regulation was investigated. The data showed that oxidative stress did not alter the total levels of GLUT1 protein, although the levels of mRNA were decreased, and there was a subcellular redistribution of GLUT1, decreasing its content at the plasma membrane. Consistently, the half-life of the protein at the plasma membrane markedly decreased under oxidative stress. The proteasome appears to be involved in GLUT1 regulation in response to oxidative stress, as revealed by an increase in stabilization of the protein present at the plasma membrane and normalization of glucose transport following proteasome inhibition. Indeed, levels of ubiquitinated GLUT1 increase as revealed by immunoprecipitation assays. Furthermore, data indicate that protein kinase B activation is involved in the stabilization of GLUT1 at the plasma membrane. Thus subcellular redistribution of GLUT1 under conditions of oxidative stress is likely to contribute to the disruption of glucose homeostasis in diabetes.

scholarly journals The protection of LingqiHuangban Granule on human retinal endothelial cells against oxidative stress-induced injury by network pharmacology

2020 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Chuandi Zhou ◽  
Deji Draga ◽  
lhamo Thashi ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Caspase 3 ◽  
Network Pharmacology ◽  
High Dose ◽  
Dependent Manner ◽  
Retinal Endothelial Cells ◽  
Holistic Treatment ◽  
Protein Protein Interaction

Abstract Background: LingqiHuangban Granule(LQHBG) is a famous traditional Chinese medicine formula used to manage retinal diseases, as an effective holistic treatment through warming Yang to exert tonifying effects on kidney and invigorating spleen to remove dampness to nourish essence of effect. The study examined protection of LQHBG on oxidative stress-induced injury in human retinal endothelial cells(HRECs) in vitro, determined the potential molecular targets of LQHBG using network pharmacology.Methods: The potential targets of active ingredients in LQHBG were predicted using pharmmapper. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out using Molecule Annotation System. The protein-protein interaction networks were constructed using Cytoscape. LQHBG was administered to rabbits to prepare medicated serum. The apoptosis of HRECs was evaluated by TUNEL and Flow Cytometry(FCM). MDA, SOD, LDH, GSH-Px, and T-AOC were detected. The mRNA expressions of Nrf2, NF-κB and HO-1 were detected, protein expression levels of Nrf2, Bcl-2, NF-κB, HO-1 and caspase-3 were analyzed.Results: TUNEL demonstrated the numbers of apoptotic cells in low-and high-dose LQHBG groups was obviously less than model group(P<0.05). FCM analysis revealed apoptotic rates of HRECs in low-and high-dose LQHBG groups were obviously reduced in a dose-dependent manner(P<0.05). The potential mechanism of LQHBG was the NF-κB pathway identified using PharmMapper. LQHBG significantly decreased MDA, LDH levels and enhanced SOD, GSH-Px and T-AOC generation. LQHBG inhibited upregulation of NF-κB, caspase-3 and enhanced Bcl-2, Nrf2, and HO-1 expression.Conclusion: LQHBG protected HRECs against oxidative-stress via suppression of apoptosis and elevation of antioxidant ability, which may involve activation of Nrf2/ARE/HO-1 pathway and inhibition of NF-κB pathway.

scholarly journals Hyperhomocysteinemia Alters Retinal Endothelial Cells Barrier Function and Angiogenic Potential via Activation of Oxidative Stress

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Riyaz Mohamed ◽  
Isha Sharma ◽  
Ahmed S. Ibrahim ◽  
Heba Saleh ◽  
Nehal M. Elsherbiny ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Barrier Function ◽  
Retinal Endothelial Cells ◽  
Angiogenic Potential

scholarly journals Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia

2021 ◽  
Vol 14 (10) ◽  
pp. 967
Author(s):  
Sibel Guzel ◽  
Charles L. Cai ◽  
Jacob V. Aranda ◽  
Kay D. Beharry
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Intermittent Hypoxia ◽  
Culture Media ◽  
Tube Formation ◽  
High Dose ◽  
Oxidative Stress Biomarkers ◽  
Vascular Permeability Factor ◽  
Retinal Endothelial Cells ◽  
And Oxidative Stress

Aquaporins (AQPs) are important for regulating cellular water, solute transport, and balance. Recently, AQPs have also been recognized as playing a key role in cell migration and angiogenesis. In the retina, hypoxia induces vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, resulting in retinal edema, which is facilitated by AQPs. Bumetanide is a diuretic agent and AQP 1–4 blocker. We tested the hypothesis that bumetanide suppression of AQPs ameliorates intermittent hypoxia (IH)-induced angiogenesis and oxidative stress in human microvascular retinal endothelial cells (HMRECs). HMRECs were treated with a low-dose (0.05 µg/mL) or high-dose (0.2 µg/mL) of bumetanide and were exposed to normoxia (Nx), hyperoxia (50% O2), or IH (50% O2 with brief hypoxia 5% O2) for 24, 48, and 72 h. Angiogenesis and oxidative stress biomarkers were determined in the culture media, and the cells were assessed for tube formation capacity and AQP-1 and -4 expression. Both doses of bumetanide significantly decreased oxidative stress and angiogenesis biomarkers. This response was reflected by reductions in tube formation capacity and AQP expression. These findings confirm the role of AQPs in retinal angiogenesis. Therapeutic targeting of AQPs with bumetanide may be advantageous for IH-induced aberrant retinal development.

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