scholarly journals Lactoferrin Induces the Synthesis of Vitamin B6 and Protects HUVEC Functions by Activating PDXP and the PI3K/AKT/ERK1/2 Pathway

2019 ◽  
Vol 20 (3) ◽  
pp. 587 ◽  
Author(s):  
Huiying Li ◽  
Yizhen Wang ◽  
Huaigu Yang ◽  
Li Liu ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Vitamin B6 ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Functional Factors ◽  
Phosphoinositide 3 Kinase ◽  
Umbilical Vein Endothelial Cells ◽  
Protein Kinase Akt ◽  
Interfering Rna ◽  
First Time ◽  
Extracellular Regulated Protein Kinases

As a nutritional active protein in foods, multiple studies of the biological activities of lactoferrin had been undertaken, including antioxidant, antiviral, anti-inflammatory, antitumor, antibiosis, and antiparasitic effects, while the mechanism related with its protection of cardiovascular system remained elusive. In the present work, the effect of lactoferrin on the viability of HUVECs (human umbilical vein endothelial cells) was detected to select the proper doses. Moreover, transcriptomics detection and data analysis were performed to screen out the special genes and the related pathways. Meanwhile, the regulation of lactoferrin in the functional factors thromboxane A2 (TXA2) and prostacyclin (PGI2) was detected. Then, the small interfering RNA (SiRNA) fragment of the selected gene pyridoxal phosphatase (PDXP) was transfected into HUVECs to validate its role in protecting HUVECs function. Results showed that lactoferrin inhibited the expression of TXA2 and activated expression of PGI2, as well as activated expression of PDXP, which significantly up-regulated the synthesis of vitamin B6 (VB6) and the phosphoinositide 3-kinase (PI3K)/ serine/threonine-protein kinase (AKT)/ extracellular regulated protein kinases (ERK) 1/2 pathway. For the first time, we revealed that lactoferrin could induce the synthesis of VB6 and protect HUVECs function through activating PDXP gene and the related pathway.

scholarly journals Compartmentalization of PDGF on extracellular binding sites dependent on exon-6-encoded sequences.

1992 ◽  
Vol 116 (2) ◽  
pp. 533-543 ◽  
Author(s):  
E W Raines ◽  
R Ross
Keyword(s):  
Smooth Muscle ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Fold Increase ◽  
Detectable Effect ◽  
Binding Studies ◽  
Alternatively Spliced ◽  
A Chain ◽  
A Charge ◽  
Umbilical Vein Endothelial Cells

The PDGFs are a family of molecules assembled as disulfide-bonded homo- and heterodimers from two distinct but highly homologous polypeptide chains (PDGF-A and PDGF-B). Two PDGF A-chain transcripts, which arise from alternative usage of the 69-bp exon 6 and exon 7, give rise to two forms of PDGF-A. In spite of the conservation of two PDGF A-chain forms over at least 350 million years, no differences in their biological activities have been identified. We have investigated the activity of the sequence encoded by the alternatively spliced exon 6 of the PDGF A-chain (peptide AL). Addition of peptide AL at 10(-5)-10(-9) M to cultured endothelium and smooth muscle induced a dose-dependent, 3-20-fold increase in PDGF in conditioned media within 30 min. Peptide AL had no detectable effect on A- or B-chain transcript levels, and decrease in culture temperature did not prevent rapid release of PDGF. In human umbilical vein endothelial cells treated with peptide AL, the PDGF release was principally PDGF-BB, while in smooth muscle cells it was primarily PDGF-AA. The capacity to induce release of PDGF is shared by the homologous peptide encoded by exon 6 of the B-chain of PDGF. Binding studies and cross-linking analysis are consistent with a charge-based association of exon 6 sequences with membrane- and matrix-associated heparan-sulfate proteoglycans. We hypothesize that translation of exon 6 of the A- or B-chain of PDGF results in compartmentalization of these forms of PDGF with HS-PG, whereas forms lacking this sequence would be soluble and diffuse.

scholarly journals Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by β1 integrins

2005 ◽  
Vol 168 (4) ◽  
pp. 643-653 ◽  
Author(s):  
Sarah M. Short ◽  
Alexandrine Derrien ◽  
Radha P. Narsimhan ◽  
Jack Lawler ◽  
Donald E. Ingber ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Endothelial Cell Migration ◽  
Vegf Receptor ◽  
Β1 Integrins ◽  
Thrombospondin 1 ◽  
Angiogenic Effect ◽  
Phosphoinositide 3 Kinase ◽  
Umbilical Vein Endothelial Cells

The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified β1 integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCγ nor Akt was necessary for this response. Furthermore, β1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that β1 integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism.

scholarly journals Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

2007 ◽  
Vol 28 (5) ◽  
pp. 1657-1668 ◽  
Author(s):  
Stéphanie Heyraud ◽  
Michel Jaquinod ◽  
Claire Durmort ◽  
Emilie Dambroise ◽  
Evelyne Concord ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Adherens Junctions ◽  
Lateral Diffusion ◽  
Cell Contact ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Annexin 2 ◽  
Umbilical Vein Endothelial Cells ◽  
Interfering Rna ◽  
Endothelial Growth Factor

ABSTRACT The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.

scholarly journals Marine Bromophenol Bis(2,3,6-Tribromo-4,5-Dihydroxybenzyl)ether Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells and Reduces Vasculogenic Mimicry in Human Lung Cancer A549 Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 641
Author(s):  
Songtao Dong ◽  
Zhongyuan Chen ◽  
Li Wang ◽  
Yankai Liu ◽  
Dimitrios Stagos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endothelial Cells ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Vasculogenic Mimicry ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Potential Candidate ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Angiogenesis, including the growth of new capillary blood vessels from existing ones and the malignant tumors cells formed vasculogenic mimicry, is quite important for the tumor metastasis. Anti-angiogenesis is one of the significant therapies in tumor treatment, while the clinical angiogenesis inhibitors usually exhibit endothelial cells dysfunction and drug resistance. Bis(2,3,6-tribromo-4,5-dihydroxybenzyl)ether (BTDE), a marine algae-derived bromophenol compound, has shown various biological activities, however, its anti-angiogenesis function remains unknown. The present study illustrated that BTDE had anti-angiogenesis effect in vitro through inhibiting human umbilical vein endothelial cells migration, invasion, tube formation, and the activity of matrix metalloproteinases 9 (MMP9), and in vivo BTDE also blocked intersegmental vessel formation in zebrafish embryos. Moreover, BTDE inhibited the migration, invasion, and vasculogenic mimicry formation of lung cancer cell A549. All these results indicated that BTDE could be used as a potential candidate in anti-angiogenesis for the treatment of cancer.

scholarly journals LINC00941 Promotes Progression of Non-Small Cell Lung Cancer by Sponging miR-877-3p to Regulate VEGFA Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Min-Huan Ren ◽  
Si Chen ◽  
Liang-Ge Wang ◽  
Wen-Xiu Rui ◽  
Pei Li
Keyword(s):  
Umbilical Vein ◽  
Tumor Development ◽  
Luciferase Assay ◽  
Small Cell Lung ◽  
Tumor Tissues ◽  
Umbilical Vein Endothelial Cells ◽  
First Time ◽  
Development Of Gastric Cancer

Long noncoding RNAs (lncRNAs) play critical roles in carcinoma occurrence and metastasis. LINC00941 has been found to mediate the development of gastric cancer, and LINC00941 was negatively associated with the longer overall survival of lung adenocarcinoma patients. Herein, our aim was to investigate the effects and mechanisms of LINC00941 in NSCLC progression. Microarray was used to identify the change lncRNAs in NSCLC, LINC00941 was found to increase in tumor tissues and patients’ plasma. Knockdown of LINC00941 didn’t modulate the proliferation of NSCLC cells, but inhibition of LINC00941 in NSCLC cells suppressed the angiogenesis ability of human umbilical vein endothelial cells (HUVECs). Moreover, LINC00941 promoted tumorigenesis in vivo, while si-LINC00941 inhibited tumor development of NSCLC. VEGFA was should to be significantly modulated by LINC00941 in NSCLC cells, then luciferase assay proved that LINC00941 regulated VEGFA expression via interacting with miR-877-3p. Followed functional experiments indicated that overexpression of LINC00941 accelerated angiogenesis and NSCLC tumor progression via miR-877-3p/VEGFA axis both in vitro and in vivo. In conclusion, our results clarified the LINC00941 function for the first time, and LINC00941 promoted the progression of NSCLC, which was mediated by miR-877-3p/VEGFA axis. This study might provide new understanding and targets for NSCLC diagnosis and treatment.

scholarly journals Characterization of Heparin Affin Regulatory Peptide Signaling in Human Endothelial Cells

2005 ◽  
Vol 280 (23) ◽  
pp. 22454-22461 ◽  
Author(s):  
Apostolos Polykratis ◽  
Panagiotis Katsoris ◽  
José Courty ◽  
Evangelia Papadimitriou
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tyrosine Phosphatase ◽  
Neuronal Cell ◽  
Cell Types ◽  
Tube Formation ◽  
Regulatory Peptide ◽  
Intracellular Signals ◽  
Umbilical Vein Endothelial Cells ◽  
Interfering Rna

Heparin affin regulatory peptide (HARP) is an 18-kDa secreted growth factor that has a high affinity for heparin and a potent role on tumor growth and angiogenesis. We have previously reported that HARP is mitogenic for different types of endothelial cells and also affects cell migration and differentiation (12). In this study we examined the signaling pathways involved in the migration and tube formation on matrigel of human umbilical vein endothelial cells (HUVEC) induced by HARP. We report for the first time that receptor-type protein-tyrosine phosphatase β/ζ (RPTPβ/ζ), which is a receptor for HARP in neuronal cell types, is also expressed in HUVEC. We also document that HARP signaling through RPTPβ/ζ leads to activation of Src kinase, focal adhesion kinase, phosphatidylinositol 3-kinase, and Erk1/2. Sodium orthovanadate, chondroitin sulfate-C, PP1, wortmannin, LY294002, and U0126 inhibit HARP-mediated signaling and HUVEC migration and tube formation. In addition, RPTPβ/ζ suppression using small interfering RNA technology interrupts intracellular signals and HUVEC migration and tube formation induced by HARP. These results establish the role of RPTPβ/ζ as a receptor of HARP in HUVEC and elucidate the HARP signaling pathway in endothelial cells.

scholarly journals Inhibitory Effect of Pelargonidin on Secretory Group IIA Phospholipase A2

2018 ◽  
Vol 13 (8) ◽  
pp. 1934578X1801300
Author(s):  
In-Chul Lee ◽  
Jong-Sup Bae
Keyword(s):  
Endothelial Cells ◽  
Phospholipase A2 ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Red Pigment ◽  
Umbilical Vein Endothelial Cells ◽  
Expression And Activity ◽  
Group Iia Phospholipase A2

The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) has been shown to be elevated in various inflammatory diseases, and lipopolysaccharide (LPS) up-regulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. Here, PEL was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Post treatment of cells or mouse with PEL inhibited LPS-induced expression and activity of sPLA2-IIA. Therefore, these results suggest that PEL inhibited LPS mediated expression of sPLA2-IIA.

scholarly journals Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner

Circulation ◽  
2007 ◽  
Vol 116 (14) ◽  
pp. 1585-1595 ◽  
Author(s):  
Ping Song ◽  
Yong Wu ◽  
Jian Xu ◽  
Zhonglin Xie ◽  
Yunzhou Dong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Small Interfering Rna ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
Chromosome 10 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Phosphatase And Tensin Homologue ◽  
Interfering Rna

Background— Oxidative stress plays a causal role in vascular injury in diabetes mellitus, but the mechanisms and targets remain poorly understood. Methods and Results— Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO − ) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Furthermore, protein kinase B/Akt inhibition induced by ONOO − or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO − . In addition, exposure of human umbilical vein endothelial cells to ONOO − or high glucose remarkably increased Ser428 phosphorylation of LKB1, a tumor suppressor. Interestingly, the ONOO − -enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA. Consistently, LKB1 phosphorylated PTEN at Ser380/Thr382/383 in vitro, suggesting that LKB1 might act as an upstream kinase for PTEN. Compared with nondiabetic mice, the levels of PTEN, LKB1-Ser428 phosphorylation, and 3-nitrotyrosine (a biomarker of ONOO − ) were significantly increased in the aortas of streptozotocin-induced diabetic mice, which was in parallel with a reduction in Akt-Ser473 phosphorylation and an increase in apoptosis. Furthermore, administration of PTEN-specific small interfering RNA suppressed diabetes-enhanced apoptosis and Akt inhibition. Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO − formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas. Conclusion— We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO − -mediated LKB1-dependent PTEN activation.

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