Arsenite Induces Endothelial Cell Permeability Increase through a Reactive Oxygen Species−Vascular Endothelial Growth Factor Pathway

2010 ◽  
Vol 23 (11) ◽  
pp. 1726-1734 ◽  
Author(s):  
Lingzhi Bao ◽  
Honglian Shi
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Permeability ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Endothelial Cell Permeability ◽  
Permeability Increase ◽  
Endothelial Growth Factor

scholarly journals Andes Virus Disrupts the Endothelial Cell Barrier by Induction of Vascular Endothelial Growth Factor and Downregulation of VE-Cadherin

2010 ◽  
Vol 84 (21) ◽  
pp. 11227-11234 ◽  
Author(s):  
Punya Shrivastava-Ranjan ◽  
Pierre E. Rollin ◽  
Christina F. Spiropoulou
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Virus Replication ◽  
Cell Permeability ◽  
Hantavirus Infection ◽  
Vascular Endothelial ◽  
Andes Virus ◽  
Endothelial Growth Factor

ABSTRACT Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) are severe diseases associated with hantavirus infection. High levels of virus replication occur in microvascular endothelial cells but without a virus-induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of these diseases. VE-cadherin is a major component of adherens junctions, and its interaction with the vascular endothelial growth factor (VEGF) receptor, VEGF-R2, is important for maintaining the integrity of the endothelial barrier. Here we report that increased secreted VEGF and concomitant decreased VE-cadherin are seen at early times postinfection of human primary lung endothelial cells with an HPS-associated hantavirus, Andes virus. Furthermore, active virus replication results in increased permeability and loss of the integrity of the endothelial cell barrier. VEGF binding to VEGF-R2 is known to result in dissociation of VEGF-R2 from VE-cadherin and in VE-cadherin activation, internalization, and degradation. Consistent with this, we showed that an antibody which blocks VEGF-R2 activation resulted in inhibition of the Andes virus-induced VE-cadherin reduction. These data implicate virus induction of VEGF and reduction in VE-cadherin in the endothelial cell permeability seen in HPS and suggest potential immunotherapeutic targets for the treatment of the disease.

scholarly journals Retinoic Acid Is a Cofactor for Translational Regulation of Vascular Endothelial Growth Factor in Human Endometrial Stromal Cells

2010 ◽  
Vol 24 (1) ◽  
pp. 148-160 ◽  
Author(s):  
Neil Sidell ◽  
Yue Feng ◽  
Lijuan Hao ◽  
Juanjuan Wu ◽  
Jie Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Endothelial Growth Factor ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Stromal Cells ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Transcriptional Activators ◽  
Endometrial Stromal Cells ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF) and endometrial angiogenesis play a critical role in successful embryonic implantation. Despite many studies of the effects of estrogen and progesterone on VEGF expression, its focal regulation at the site of implantation is unknown. Retinoic acid (RA) has been reported to regulate VEGF in a variety of cell types. Because localized RA synthesis occurs within the periimplantation endometrium, we tested the possibility that RA regulates VEGF production in endometrial stromal cells. Using primary and telomerase-immortalized human endometrial stromal cells, we determined that RA alone did not alter constitutive levels of VEGF production, but markedly amplified secretion when the cells were cotreated with activators of VEGF gene transcription (12-O-tetradecanoyl phorbol-13-acetate, TPA; TGF-β; and IL-1β). Whereas TPA or TGF-β alone stimulated VEGF promoter activity and up-regulated mRNA levels, significant protein secretion was detected only after RA was added to the culture systems. Analysis of retinoids in secretory phase endometrial biopsies indicated that endogenous RA accumulated at concentrations sufficient to induce VEGF secretion. Polyribosome profile analysis showed that the addition of RA to transcriptional activators of VEGF shifted the translational suppressed VEGF mRNA transcripts into larger polyribosome complexes engaged in active translation. Although the precise mechanism(s) of the RA effect remains to be defined, it appears to be mediated by reactive oxygen species; the antioxidant N-acetylcysteine inhibited RA+TPA-stimulated secretion of VEGF by more than 80%. Together, our results demonstrate that in human endometrial stromal cells, RA can combine with transcriptional activators of VEGF to augment VEGF secretion through a translational mechanism of action mediated by reactive oxygen species. These findings suggest a link between the spatiotemporal changes of retinoid synthesis in the periimplantation stroma and the capacity to quickly up-regulate focal VEGF secretion needed to induce early angiogenic events of pregnancy.

scholarly journals Roles of Reactive Oxygen Species in Anticancer Therapy withSalvia miltiorrhiza Bunge

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Chiang Hung ◽  
Tai-Long Pan ◽  
Wen-Long Hu
Keyword(s):  
Reactive Oxygen Species ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Anticancer Therapy ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Endothelial Growth Factor

Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy withSalvia miltiorrhizaBunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

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