scholarly journals Effects of 5-Hydroxymethylcytosine Epigenetic Modification on the Stability and Molecular Recognition of VEGF i-Motif and G-Quadruplex Structures

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Rhianna K. Morgan ◽  
Michael M. Molnar ◽  
Harshul Batra ◽  
Bethany Summerford ◽  
Randy M. Wadkins ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Epigenetic Modification ◽  
Antiangiogenic Therapy ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
G Quadruplex ◽  
Physicochemical Effect ◽  
The Stability ◽  
Epigenetic Modulation ◽  
Endothelial Growth Factor

Promoters often contain asymmetric G- and C-rich strands, in which the cytosines are prone to epigenetic modification via methylation (5-mC) and 5-hydroxymethylation (5-hmC). These sequences can also form four-stranded G-quadruplex (G4) or i-motif (iM) secondary structures. Although the requisite sequences for epigenetic modulation and iM/G4 formation are similar and can overlap, they are unlikely to coexist. Despite 5-hmC being an oxidization product of 5-mC, the two modified bases cluster at distinct loci. This study focuses on the intersection of G4/iM formation and 5-hmC modification using the vascular endothelial growth factor (VEGF) gene promoter’s CpG sites and examines whether incorporation of 5-hmC into iM/G4 structures had any physicochemical effect on formation, stability, or recognition by nucleolin or the cationic porphyrin, TMPyP4. No marked changes were found in the formation or stability of iM and G4 structures; however, changes in recognition by nucleolin or TMPyP4 occurred with 5-hmC modification wherein protein and compound binding to 5-hmC modified G4s was notably reduced. G4/iM structures in the VEGF promoter are promising therapeutic targets for antiangiogenic therapy, and this work contributes to a comprehensive understanding of their governing principles related to potential transcriptional control and targeting.

scholarly journals Lipid Raft Association Stabilizes VEGF Receptor 2 in Endothelial Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 798
Author(s):  
Ibukunoluwapo O. Zabroski ◽  
Matthew A. Nugent
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Lipid Rafts ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Potential Mechanism ◽  
Lysosomal Degradation ◽  
Extracellular Signal ◽  
The Stability ◽  
Endothelial Growth Factor

The binding of vascular endothelial growth factor A (VEGF) to VEGF receptor-2 (VEGFR-2) stimulates angiogenic signaling. Lipid rafts are cholesterol-dense regions of the plasma membrane that serve as an organizational platform for biomolecules. Although VEGFR2 has been shown to colocalize with lipid rafts to regulate its activation, the effect of lipid rafts on non-activated VEGFR2 has not been explored. Here, we characterized the involvement of lipid rafts in modulating the stability of non-activated VEGFR2 in endothelial cells using raft disrupting agents: methyl-β-cyclodextrin, sphingomyelinase and simvastatin. Disrupting lipid rafts selectively decreased the levels of non-activated VEGFR2 as a result of increased lysosomal degradation. The decreased expression of VEGFR2 translated to reduced VEGF-activation of the extracellular signal-regulated protein kinases (ERK). Overall, our results indicate that lipid rafts stabilize VEGFR2 and its associated signal transduction activities required for angiogenesis. Thus, modulation of lipid rafts may provide a means to regulate the sensitivity of endothelial cells to VEGF stimulation. Indeed, the ability of simvastatin to down regulate VEGFR2 and inhibit VEGF activity suggest a potential mechanism underlying the observation that this drug improves outcomes in the treatment of certain cancers.

scholarly journals Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway

2010 ◽  
Vol 235 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Grzegorz Korpanty ◽  
Elizabeth Smyth ◽  
Laura A Sullivan ◽  
Rolf A Brekken ◽  
Desmond N Carney
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antiangiogenic Therapy ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation

2008 ◽  
Vol 197 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Angélica Morales ◽  
Sumiko Morimoto ◽  
Lorenza Díaz ◽  
Guillermo Robles ◽  
Vicente Díaz-Sánchez
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pancreatic Tissue ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Rinm5f Cells ◽  
Vegf Gene ◽  
Rat Pancreas ◽  
Endothelial Growth Factor

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

scholarly journals Polymorphism in the regulatory regions –С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis

2017 ◽  
Vol 89 (5) ◽  
pp. 60-64 ◽  
Author(s):  
A V Shevchenko ◽  
V F Prokofyev ◽  
M A Korolev ◽  
N E Banshchikova ◽  
V I Konenkov
Keyword(s):  
Rheumatoid Arthritis ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Polymorphism Analysis ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Regulatory Regions ◽  
Female Patients ◽  
Healthy Women ◽  
Endothelial Growth Factor

Aim. To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. Results. There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. Conclusion. The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

scholarly journals Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 52 (05) ◽  
pp. 264-279
Author(s):  
Xiaorong Li ◽  
Juping Liu ◽  
Qianhui Yang ◽  
Yan Zhang ◽  
Xiaomin Zhang
Keyword(s):  
Diabetic Retinopathy ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Vegf Gene ◽  
Asian Populations ◽  
Increased Risk ◽  
Endothelial Growth Factor

AbstractThe associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) – proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) – remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.

Sign in / Sign up

Export Citation Format

Share Document