Endothelial cells' biophysical, biochemical, and chromosomal aberrancies in high-glucose condition within the diabetic range

2017 ◽  
Vol 35 (2) ◽  
pp. 83-97 ◽  
Author(s):  
Aysa Rezabakhsh ◽  
Elahe Nabat ◽  
Mina Yousefi ◽  
Soheila Montazersaheb ◽  
Omid Cheraghi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
High Glucose Condition ◽  
Glucose Condition

scholarly journals RUNX1 can mediate the glucose and O-GlcNAc-driven proliferation and migration of human retinal microvascular endothelial cells

2021 ◽  
Vol 9 (1) ◽  
pp. e001898
Author(s):  
Xindan Xing ◽  
Hanying Wang ◽  
Tian Niu ◽  
Yan Jiang ◽  
Xin Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Tube Formation ◽  
Cell Counting ◽  
Microvascular Endothelial Cells ◽  
High Glucose Condition ◽  
Microvascular Endothelial ◽  
And Migration ◽  
Glucose Condition ◽  
Proliferation And Migration

IntroductionThis study aims to determine whether high glucose condition and dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification can promote the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) and whether Runt-related transcription factor 1 (RUNX1) could mediate the glucose and O-GlcNAc-driven proliferation and migration of HRMECs.Research design and methodsWestern blot analysis was used to detect the O-GlcNAc modification level and RUNX1 level in cells and retina tissues, cell growth was studied by cell counting kit-8 assay, cell proliferation was detected by immunofluorescence staining. Then, cell migration and tube formation were investigated by scratch-wound assay, Transwell assay, and tube-forming assay. The changes of retinal structure were detected by H&E staining. The O-GlcNAc modification of RUNX1 was detected by immunoprecipitation.ResultsHigh glucose increases pan-cellular O-GlcNAc modification and the proliferation and migration of HRMECs. Hence, O-GlcNAc modification is critical for the proliferation and migration of HRMECs. RUNX1 mediates the glucose and O-GlcNAc-driven proliferation and migration in HRMECs. RUNX1 can be modified by O-GlcNAc, and that the modification is enhanced in a high glucose environment.ConclusionsThe present study reveals that high glucose condition directly affects retinal endothelial cells (EC) function, and O-GlcNAc modification is critical for the proliferation and migration of HRMECs, RUNX1 may take part in this mechanism, and maybe the function of RUNX1 is related to its O-GlcNAc modification level, which provides a new perspective for studying the mechanism of RUNX1 in diabetic retinopathy.

scholarly journals High Glucose Treatment Limits Drosha Protein Expression and Alters AngiomiR Maturation in Microvascular Primary Endothelial Cells via an Mdm2-dependent Mechanism

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 742
Author(s):  
Brian Lam ◽  
Emmanuel Nwadozi ◽  
Tara L. Haas ◽  
Olivier Birot ◽  
Emilie Roudier
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Protein Expression ◽  
High Glucose ◽  
Micro Rna ◽  
Microvascular Endothelium ◽  
High Glucose Condition ◽  
Mdm2 Expression ◽  
Dicer Protein ◽  
Glucose Condition

Diabetes promotes an angiostatic phenotype in the microvascular endothelium of skeletal muscle and skin. Angiogenesis-related microRNAs (angiomiRs) regulate angiogenesis through the translational repression of pro- and anti-angiogenic genes. The maturation of micro-RNA (miRs), including angiomiRs, requires the action of DROSHA and DICER proteins. While hyperglycemia modifies the expression of angiomiRs, it is unknown whether high glucose conditions alter the maturation process of angiomiRs in dermal and skeletal muscle microvascular endothelial cells (MECs). Compared to 5 mM of glucose, high glucose condition (30 mM, 6–24 h) decreased DROSHA protein expression, without changing DROSHA mRNA, DICER mRNA, or DICER protein in primary dermal MECs. Despite DROSHA decreasing, high glucose enhanced the maturation and expression of one angiomiR, miR-15a, and downregulated an miR-15a target: Vascular Endothelial Growth Factor-A (VEGF-A). The high glucose condition increased Murine Double Minute-2 (MDM2) expression and MDM2-binding to DROSHA. Inhibition of MDM2 prevented the effects evoked by high glucose on DROSHA protein and miR-15a maturation in dermal MECs. In db/db mice, blood glucose was negatively correlated with the expression of skeletal muscle DROSHA protein, and high glucose decreased DROSHA protein in skeletal muscle MECs. Altogether, our results suggest that high glucose reduces DROSHA protein and enhances the maturation of the angiostatic miR-15a through a mechanism that requires MDM2 activity.

scholarly journals Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition

Bioimpacts ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 219-226 ◽  
Author(s):  
Aysa Rezabakhsh ◽  
Soheila Montazersaheb ◽  
Elahe Nabat ◽  
Mehdi Hassanpour ◽  
Azadeh Montaseri ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
High Glucose Condition ◽  
Glucose Condition

Abstract 169: Impaired Shear Stress-induced Endothelial Nitric Oxide Production in High Glucose Condition is Restored by Inhibiton via NADPH Consumption by Polyol Pathway Activation

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Tomio Umemoto ◽  
Masatoshi Kuroki ◽  
Hiroto Ueba ◽  
Masanobu Kawakami ◽  
Hideo Fujita ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Polyol Pathway ◽  
No Production ◽  
Pathway Activation ◽  
High Glucose Condition ◽  
Glucose Condition

Endothelial dysfunction leading to cardiovascular disease risk involves a decrease in nitric oxide (NO) production. In physiological conditions shear stress is a potent stimulation of endothelium-derived NO production and flow mediated NO production is regulated by the activation of endothelial NO synthase (eNOS). In endothelial cells, eNOS, aldose reductase (AR), a rate limiting enzyme of polyol pathway, and glutathione reductase (GR) share a NADPH as an obligate cofactor. In diabetec condition intracellular polyol pathway is activated and this may decrease shear stress-induced endothelial NO production and increase intracellular oxidative stress via inhibition of eNOS and GR by NADPH consumption. Therefore we investigated whethter AR inhibitor epalrestat improved endothelial NO production under high glucose condition to elucidate the mechanism of endothelial dysfunction in diabetes. We incubated human umbilical vein endothelial cells (HUVECs) in normal (5mM) and high (30mM) glucose condition for 72 hours, with or without epralrestat, or 100U/ml superoxide dismutase (SOD), respectively. After exchange of medium for Krebs’ buffer, HUVECs were exposed to 12dyne/cm2 steady laminar fluid shear stress for 5 minutes. NO release from HUVECs was measured as NO2 using a NOx analyzing HPLC system by Griess reaction. Next we harvested the cells in lysis buffer and analyzed phosphorylation of Akt (shear induced intracellular signal transduction) and eNOS by western blotting, and measured intracellular 8-OHdG and ratio of NADPH/NADP. In high glucose condition NO2 was decreased and 8-OHdG increased compared to low glucose. NO2 was restored and 8-OHdG was reduced by epalrestat significantly (p<0.01, p<0.05, respectively, vs. high glucose condition). In SOD-treated HUVECs, NO2 was not restored (n.s. vs. high glucose condition) despite of complete reduction of 8-OHdG (p<0.01). Both Akt and eNOS phosphorylation by shear stress was affected neither by high glucose, epalrestat nor SOD. Intracellular NADPH/NADP ratio was decreased in high glucose condition, but this reduction was restored by epalrestat. These results showed that polyol pathway activation plays a key role in endothelial NO production under high glucose condition via a cofactor NADPH.

Effect of metformin and celecoxib on cytotoxicity and release of GDF-15 from human mesenchymal stem cells in high glucose condition

2017 ◽  
Vol 35 (7) ◽  
pp. 407-413 ◽  
Author(s):  
Elaheh Zafarvahedian ◽  
Azam Roohi ◽  
Mohammad Reza Sepand ◽  
Seyed Nasser Ostad ◽  
Mohammad Hossein Ghahremani
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Human Mesenchymal Stem Cells ◽  
High Glucose Condition ◽  
Glucose Condition
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