Peroxynitrite modulates receptor-activated Ca2+ signaling in vascular endothelial cells

1996 ◽  
Vol 270 (6) ◽  
pp. L954-L961 ◽  
Author(s):  
S. J. Elliott
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
No Donor ◽  
Time Points ◽  
Inactive Metabolite ◽  
Spermine Nonoate

Peroxynitrite (ONOO-) is formed from superoxide (O2-) and .NO. We have previously reported that O2- does not alter endothelial cell Ca2+ signaling. To test whether .NO alters Ca2+ signaling, cells were incubated with the .NO donor, spermine NONOate. Neither spermine NONOate nor S-nitroso-N-acetyl penicillamine (SNAP) altered bradykinin-stimulated Ca2+ signaling. By contrast, 3-morpholinosydnonimine (SIN-1), which generates ONOO- by releasing O2- and .NO essentially in a simultaneous manner, significantly inhibited signaling. Initially, the inhibitory effect of 1 mM SIN-1 was selective toward agonist-stimulated influx of external Ca2+. At later time points, SIN-1 additionally depleted internal stores of releasable Ca2+. When cells were coincubated with SIN-1 plus superoxide dismutase, a technique designed to scavenge O2- and convert SIN-1 to purely an .NO-donor compound, Ca2+ signaling was identical to control. SIN-1C, the inactive metabolite of SIN-1, had no effect on [Ca2+]i. This study demonstrates that exogenously generated ONOO- modulates endothelial cell Ca2+ signaling, suggesting that ONOO- is of biological relevance to vasoregulation.

scholarly journals Oxidant stress inhibits the store-dependent Ca2+-influx pathway of vascular endothelial cells

1993 ◽  
Vol 292 (2) ◽  
pp. 385-393 ◽  
Author(s):  
S J Elliott ◽  
T N Doan
Keyword(s):  
Endothelial Cells ◽  
Direct Effect ◽  
Vascular Endothelial Cells ◽  
Oxidant Stress ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Butyl Hydroperoxide ◽  
Time Points ◽  
Fura 2

Oxidant stress induced by t-butyl hydroperoxide (t-BuOOH) inhibits bradykinin-stimulated Ca2+ signalling in vascular endothelial cells. The effect of t-BuOOH on intracellular Ca2+ pools was determined by addition of Ca(2+)-releasing agents to fura-2-loaded cells suspended in Ca(2+)-free/EGTA buffer. In control cells, sequential additions of bradykinin and ionomycin produced similar increases in cytosolic free [Ca2+] ([Ca2+]i). By contrast, incubation with t-BuOOH progressively decreased the response of [Ca2+]i to bradykinin and increased that to ionomycin, suggesting that the total (ionomycin-releasable) Ca2+ pool remains replete during oxidant stress. The effect of t-BuOOH on the InsP3-sensitive Ca2+ pool was measured by the increase in [Ca2+]i or efflux of 45Ca2+ stimulated by 2,5-di-t-butylhydroquinone (BHQ). Incubation with t-BuOOH did not inhibit BHQ-stimulated increases in [Ca2+]i or 45Ca2+ efflux, suggesting that the InsP3-sensitive Ca2+ pool remains replete and releasable. Activity of the Ca(2+)-influx pathway stimulated by release of internal Ca2+ stores was determined via re-addition of Ca2+ to BHQ-stimulated cells suspended in Ca(2+)-free/EGTA buffer and via BHQ-stimulated 45Ca2+ uptake. Incubation of cells with t-BuOOH for 1 h significantly inhibited the influx pathway. At later time points, t-BuOOH increased basal [Ca2+]i and potentiated the response of [Ca2+]i to BHQ. Similar results were demonstrated with thapsigargin. Together, these findings suggest that (1) the inhibitory effect of t-BuOOH on bradykinin-stimulated release of Ca2+ from internal stores is not related to depletion of these stores, and (2) inhibition of the store-dependent Ca(2+)-influx pathway occurs by a direct effect of the influx pathway or by inhibition of the mechanism which links the internal Ca2+ store to plasmalemmal Ca2+ influx.

The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate

1988 ◽  
Vol 60 (02) ◽  
pp. 226-229 ◽  
Author(s):  
Jerome M Teitel ◽  
Hong-Yu Ni ◽  
John J Freedman ◽  
M Bernadette Garvey
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Monolayer Cultures ◽  
Coagulant Activity ◽  
Time Courses ◽  
Privileged Site

SummarySome classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

scholarly journals miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jizhi Wu ◽  
Guangqi Zhang ◽  
Hui Xiong ◽  
Yuguang Zhang ◽  
Gang Ding ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxygen Therapy ◽  
Vascular Endothelial Cells ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Endothelial Cells ◽  
Nasal Inhalation ◽  
Induced Apoptosis

AbstractOxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

scholarly journals Inhibitory effect of caveolin-1 in vascular endothelial cells, pericytes and smooth muscle cells

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76165-76173 ◽  
Author(s):  
Hongping Xu ◽  
Liwei Zhang ◽  
Wei Chen ◽  
Jiazhou Xu ◽  
Ruting Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Endothelial Cells ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Caveolin 1

scholarly journals Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells.

1996 ◽  
Vol 183 (2) ◽  
pp. 569-579 ◽  
Author(s):  
M Salmi ◽  
S Jalkanen
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Lymphoid Tissues ◽  
Vascular Endothelial ◽  
Adhesion Protein ◽  
Culture Model ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP- 1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.

Sign in / Sign up

Export Citation Format

Share Document