scholarly journals Bavachalcone Enhances RORαExpression, Controls Bmal1 Circadian Transcription, and Depresses Cellular Senescence in Human Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Yanqi Dang ◽  
Shuang Ling ◽  
Jing Ma ◽  
Rongzhen Ni ◽  
Jin-Wen Xu
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Replicative Senescence ◽  
Orphan Receptor ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Orphan Nuclear Receptor ◽  
Human Endothelial Cells ◽  
Peripheral Tissues ◽  
Natural Medicine

The circadian clock regulates many aspects of (patho)physiology in the central nervous system and in the peripheral tissues. RAR-related orphan receptorα(RORα), an orphan nuclear receptor, is involved in circadian rhythm regulation, including regulation of cardiovascular function. Bavachalcone, a prenylchalcone, is a major bioactive chalcone isolated fromPsoralea corylifolia. This natural ingredient activated RORα1 luciferase reporter activity on drug screening. In addition, bavachalcone induced RORα1 expression in mRNA and protein levels in a dose-dependent manner and enhanced the circadian amplitude of Bmal1 mRNA expression after serum shock. Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression ofp16ink4a(a marker of replicative senescence) and IL-1α(a proinflammatory cytokine of the senescence-associated secretory phenotype). These inhibitory effects were partially reversed by the RORαinhibitor VPR-66. Our results demonstrate that bavachalcone, as a natural medicine ingredient, has a pharmacological function in regulating RORα1.

scholarly journals Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

2006 ◽  
Vol 191 (1) ◽  
pp. 171-177 ◽  
Author(s):  
Lachlan J Pearson ◽  
Christopher Rait ◽  
M Gary Nicholls ◽  
Timothy G Yandle ◽  
John J Evans
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Sex Steroids ◽  
Vascular Endothelial Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Human Endothelial Cells ◽  
Concentration Dependent Manner ◽  
Aortic Endothelial Cells

It is well documented that there are gender differences in the incidence and patterns of cardiovascular diseases but the reasons are unclear. Sex steroids may modulate the behaviour of vascular endothelial cells, which in turn act by paracrine processes to alter adjacent vascular smooth muscle activity. We hypothesised that the sex steroids alter the percentage of vascular endothelial cells that secrete the vasodilator peptide, adrenomedullin and modify the adrenomedullin-stimulating action of angiotensin-II. The percentage of adrenomedullin-secreting human aortic endothelial cells was determined using the cell immunoblot method. Cells were incubated with selected concentrations of angiotensin-II, oestradiol and testosterone alone and sex steroids in combination with angiotensin-II. Adrenomedullin mRNA expression in endothelial cells was quantified by real-time PCR. It was observed that at 4 h, angiotensin-II increased the percentage of adrenomedullin-secreting cells in a concentration-dependent manner. Testosterone at physiological concentrations was observed to increase the number of adrenomedullin-secreting cells whilst oestradiol had no effect. Addition of testosterone to angiotensin-II resulted in less than additive increases in the number of cells secreting adrenomedullin. Oestradiol reduced the angiotensin-II-induced increase in adrenomedullin-secreting cells. Adrenomedullin mRNA expression was significantly increased by testosterone and there was also a trend for an increase in adrenomedullin mRNA expression, which occurred when cells were incubated with angiotensin-II. Our results point to a complex interplay between the sex steroids and angiotensin-II in regulating adrenomedullin production by human endothelial cells, which may contribute to gender-related differences in vascular disease in humans.

Chunghyuldan activates NOS mRNA expression and suppresses VCAM-1 mRNA expression in human endothelial cells

2005 ◽  
Vol 83 (12) ◽  
pp. 1101-1108 ◽  
Author(s):  
Seong-Uk Park ◽  
Woo-Sang Jung ◽  
Sang-Kwan Moon ◽  
Chang-Nam Ko ◽  
Ki-Ho Cho ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Stroke Recurrence ◽  
No Production ◽  
Clinical Effects ◽  
Dependent Manner ◽  
Human Endothelial Cells ◽  
Synthesis Inhibitor ◽  
Anti Inflammatory

Chunghyuldan (CHD), a combinatorial drug that has antihyperlipidemic and anti-inflammatory activities, has been shown to improve arterial stiffness and inhibit stroke recurrence in clinical study. To understand the molecular basis of CHD's clinical effects, we explored its effect on cell proliferation and expression of nitric oxide synthase (NOS) and vascular cell adhesion molecule (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Cell number counting and [3H]thymidine incorporation assay demonstrated that nontoxic doses of CHD have an inhibitory effect on DNA synthesis and suppress cell cycle progression of HUVECs. CHD treatment led to a marked induction of NO production through up-regulation of NOS mRNA expression in a dose- and time-dependent manner, whereas it suppressed VCAM-1 expression. CHD inhibition of VCAM-1 expression was totally blocked by pretreatment with the NO synthesis inhibitor L-NMMA, whereas pretreatment with the NO donor DETA-NO further decreased VCAM-1 level in CHD-treated HUVECs, indicating that VCAM-1 regulation by CHD is mediated through increased NO synthesis by CHD. In addition, TNF-α-mediated VCAM-1 activation was substantially impeded by CHD treatment. Collectively, our data suggest that anti-inflammatory or anti-hyperlipidemic effects of CHD might be associated with its ability to activate NO production and suppress VCAM-1 expression in human endothelial cells.

Hemoglobin Enhances the Binding of Bacterial Endotoxin to Human Endothelial Cells

1996 ◽  
Vol 76 (02) ◽  
pp. 258-262 ◽  
Author(s):  
Robert I Roth
Keyword(s):  
Endothelial Cells ◽  
Binding Protein ◽  
Bacterial Endotoxin ◽  
Dependent Manner ◽  
Serum Free Medium ◽  
Free Medium ◽  
Human Endothelial Cells ◽  
Serum Factors ◽  
Serum Free ◽  
Lps Binding

SummaryHuman endothelial cells, when incubated with bacterial endotoxin (lipopolysaccharide, LPS), modify their surface in association with prominent production of procoagulant tissue factor (TF) activity. This deleterious biological effect of LPS has been shown previously to be enhanced approximately 10-fold by the presence of hemoglobin (Hb), a recently recognized LPS binding protein that causes disaggregation of LPS and increases the biological activity of LPS in a number of in vitro assays. The present study was performed to test the hypothesis that Hb enhances the LPS-induced procoagulant activity of human umbilical vein endothelial cells (HUVEC) by increasing LPS binding to the cells. The binding of 3H-LPS to HUVEC was determined in the absence or presence of Hb or two other known LPS-binding proteins, human serum albumin (HSA) and IgG. LPS binding was substantially increased in the presence of Hb, in a Hb concentration-dependent manner, but was not increased by HSA or IgG. Hb enhancement of LPS binding was observed in serum-free medium, indicating that there was no additional requirement for any of the serum factors known to participate in the interaction of LPS with cells (e.g., lipopolysaccharide (LPS)-binding protein (LBP) and soluble CD14 (sCD14)). Hb enhancement of LPS binding also was observed in the more physiologic condition of 100% plasma. LPS-induced TF activity was stimulated by Hb, but not by HSA or IgG. In serum-free medium, TF activity was not stimulated under any of the conditions tested. Ultrafiltration of LPS was dramatically increased after incubation with Hb but not with HSA or IgG, suggesting that LPS disaggregation by Hb was responsible for the enhanced binding of LPS to HUVEC and the subsequent stimulation of TF activity.

scholarly journals Cyclooxygenase-2 Glycosylation Is Affected by Peroxynitrite in Endothelial Cells: Impact on Enzyme Activity and Degradation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 496
Author(s):  
Sonia Eligini ◽  
Susanna Colli ◽  
Aida Habib ◽  
Giancarlo Aldini ◽  
Alessandra Altomare ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Cyclooxygenase 2 ◽  
Nitric Oxide Donors ◽  
Metabolic Labeling ◽  
Dependent Manner ◽  
De Novo Synthesis ◽  
Human Endothelial Cells ◽  
Prolonged Incubation ◽  
Cox 2

The exposure of human endothelial cells to 3-morpholinosydnonimine (SIN-1) induced the expression of cyclooxygenase-2 (COX-2) in a dose- and time-dependent manner. Interestingly, after a prolonged incubation (>8 h) several proteoforms were visualized by Western blot, corresponding to different states of glycosylation of the protein. This effect was specific for SIN-1 that generates peroxynitrite and it was not detected with other nitric oxide-donors. Metabolic labeling experiments using 35S or cycloheximide suggested that the formation of hypoglycosylated COX-2 was dependent on de novo synthesis of the protein rather than the deglycosylation of the native protein. Moreover, SIN-1 reduced the activity of the hexokinase, the enzyme responsible for the first step of glycolysis. The hypoglycosylated COX-2 induced by SIN-1 showed a reduced capacity to generate prostaglandins and the activity was only partially recovered after immunoprecipitation. Finally, hypoglycosylated COX-2 showed a more rapid rate of degradation compared to COX-2 induced by IL-1α and an alteration in the localization with an accumulation mainly detected in the nuclear membrane. Our results have important implication to understand the effect of peroxynitrite on COX-2 expression and activity, and they may help to identify new pharmacological tools direct to increase COX-2 degradation or to inhibit its activity.

scholarly journals The Hypoxia-Inducible Factor 1/NOR-1 Axis Regulates the Survival Response of Endothelial Cells to Hypoxia

2009 ◽  
Vol 29 (21) ◽  
pp. 5828-5842 ◽  
Author(s):  
Lluis Martorell ◽  
Maurizio Gentile ◽  
Jordi Rius ◽  
Cristina Rodríguez ◽  
Javier Crespo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Orphan Receptor ◽  
Vegf Receptor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Hypoxia Inducible Factor 1 ◽  
Apoptosis Protein

ABSTRACT Hypoxia induces apoptosis but also triggers adaptive mechanisms to ensure cell survival. Here we show that the prosurvival effects of hypoxia-inducible factor 1 (HIF-1) in endothelial cells are mediated by neuron-derived orphan receptor 1 (NOR-1). The overexpression of NOR-1 decreased the rate of endothelial cells undergoing apoptosis in cultures exposed to hypoxia, while the inhibition of NOR-1 increased cell apoptosis. Hypoxia upregulated NOR-1 mRNA levels in a time- and dose-dependent manner. Blocking antibodies against VEGF or SU5614 (a VEGF receptor 2 inhibitor) did not prevent hypoxia-induced NOR-1 expression, suggesting that NOR-1 is not induced by the autocrine secretion of VEGF in response to hypoxia. The reduction of HIF-1α protein levels by small interfering RNAs, or by inhibitors of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway or mTOR, significantly counteracted hypoxia-induced NOR-1 upregulation. Intracellular Ca2+ was involved in hypoxia-induced PI3K/Akt activation and in the downstream NOR-1 upregulation. A hypoxia response element mediated the transcriptional activation of NOR-1 induced by hypoxia as we show by transient transfection and chromatin immunoprecipitation assays. Finally, the attenuation of NOR-1 expression reduced both basal and hypoxia-induced cIAP2 (cellular inhibitor of apoptosis protein 2) mRNA levels, while NOR-1 overexpression upregulated cIAP2. Therefore, NOR-1 is a downstream effector of HIF-1 signaling involved in the survival response of endothelial cells to hypoxia.

scholarly journals MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury

2019 ◽  
Vol 25 (7) ◽  
pp. 433-443
Author(s):  
Lin-Lin Feng ◽  
Wei-Na Xin ◽  
Xiu-Li Tian
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Combined Treatment ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Inflammatory Injury ◽  
Tnf Α ◽  
Microvascular Endothelial

To investigate the role of miR-146 and its possible relationship with MALAT1 in LPS-induced inflammation in human microvascular endothelial cells (HMECs), HMEC-1 cells were treated with LPS to construct an inflammatory injury cell model, and the cell viability, TNF-α and IL-6 secretion and the expression levels of VCAM-1, SELE and ICAM-1 were analysed as markers of inflammatory injury. The regulation mechanisms of miR-146 interacted with MALAT1 and the downstream NF-κB signalling were also verified by dual-luciferase assay and knockdown technology. LPS significantly decreased the cell viability, increased levels of VCAM-1, SELE and ICAM-1 and also up-regulated miR-146a/b, TNF-α and IL-6 in a dose-dependent manner. Over-expression of miR-146a resulted in down-regulation of TNF-α and IL-6, as well as VCAM-1, SELE and ICAM-1, while inhibition of miR-146a led to opposite results. The dual-luciferase reporter assay showed both miR-146a and miR-146b directly targeted and negatively regulated the expression of MALAT1. Silencing of MALAT1 suppressed LPS-induced NF-κB activation and TNF-α and IL-6 secretion, reducing the cell inflammatory injury, but these changes were reversed after combined treatment with miR-146a inhibitor. Taken together, we demonstrate that miR-146 protects HMECs against inflammatory injury by inhibiting NF-κB activation. This process is modulated by MALAT1.

scholarly journals Erythropoietin receptor mRNA expression in human endothelial cells.

1994 ◽  
Vol 91 (9) ◽  
pp. 3974-3978 ◽  
Author(s):  
A. Anagnostou ◽  
Z. Liu ◽  
M. Steiner ◽  
K. Chin ◽  
E. S. Lee ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Erythropoietin Receptor ◽  
Human Endothelial Cells ◽  
Receptor Mrna

Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis

2001 ◽  
Vol 36 (8) ◽  
pp. 1327-1347 ◽  
Author(s):  
Mechthild Wagner ◽  
Barbara Hampel ◽  
David Bernhard ◽  
Monika Hala ◽  
Werner Zwerschke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Replicative Senescence ◽  
G1 Arrest ◽  
Human Endothelial Cells

scholarly journals The Helix–Loop–Helix Protein Id-1 Delays Onset of Replicative Senescence in Human Endothelial Cells

2002 ◽  
Vol 82 (8) ◽  
pp. 1073-1079 ◽  
Author(s):  
Jun Tang ◽  
Gabriel M Gordon ◽  
Brian J Nickoloff ◽  
Kimberly E Foreman
Keyword(s):  
Endothelial Cells ◽  
Replicative Senescence ◽  
Human Endothelial Cells ◽  
Helix Loop Helix
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