Airborne Quinones Caused Cytotoxicity and DNA Damage in Human Vascular Endothelial Cells

Traffic-related particulate matter (PM) is found to be associated with adverse cardiovascular diseases. Quinones present in the traffic-related PM are hypothesized to contribute to these harmful effects through reactive oxygen species (ROS) generation. However, the impacts of the airborne quinones on the cytotoxic and genotoxic effects in human vascular endothelial cells are less well known. The aim of the present study is to assess whether exposure to three typical airborne quinones, including anthraquinone (AQ), 1,4-naphthroquinone (NQ) and benzoquinone (BQ), can induce cytotoxicity and DNA damage in the human umbilical vein endothelial cells (HUVEC). Cell viability, plasma membrane damage (lactate dehydrogenase leakage), and DNA damage were assessed in HUVEC after exposed to the three airborne quinones. Significant cytotoxicity was caused by the three quinones, indicating by the significant decrease in cell viability and significant increase in LDH activity. AQ and BQ slightly increased the DNA damage in HUVEC without significance. The ROS generation was not observed in HUVEC after exposed to AQ, NQ or BQ, suggesting that the cyototoxicity and the DNA damage caused by these quinones in HUVEC were not generated through the oxidative stress pathway. Our results suggest that AQ, NQ and BQ presented in the traffic-related particles may participate in the development of cardiovascular diseases through causing cytotoxicity and DNA damage in vascular endothelial cells.

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Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells

Scientific Reports ◽

10.1038/s41598-019-46236-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Hitomi Miyake ◽

Dai Miyazaki ◽

Yumiko Shimizu ◽

Shin-ichi Sasaki ◽

Takashi Baba ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Viability ◽

Esterase Activity ◽

Vascular Endothelial Cells ◽

Membrane Damage ◽

Retinal Vasculitis ◽

Retinal Toxicity ◽

Diaminopimelic Acid ◽

Vascular Endothelial ◽

Vascular Cells

Abstract Prophylactic intracameral injection of antibiotics is commonly used to prevent endophthalmitis after cataract surgery. However, devastating visual complications have been reported including hemorrhagic occlusive retinal vasculitis (HORV).To determine the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular cells, human retinal vascular endothelial cells (RVEC) and pericytes were exposed to three antibiotics, and the adverse effects were assessed by membrane damage, loss of intrinsic esterase activity, kinetic cell viability, and inflammatory cytokine secretion. Their retinal toxicity was examined by live/dead assays after an intravitreal injection of the three antibiotics into mice eyes. In vascular cells in culture, membrane damage and loss of esterase activity were induced after exposure to the three antibiotics. The toxic effects were most obvious after moxifloxacin (RVEC, ≥125 μg/mL; pericytes, ≥1000 μg/mL) at 24 h. Cefuroxime also reduced esterase activity and the membrane integrity of vascular cells but were less toxic than moxifloxacin. Kinetic cell viability testing showed that 500 μg/mL of moxifloxacin exposure induced significant decrease (29%) in the viability as early as 1 h. When the inflammatory effects of the antibiotics were examined, a significant induction of IL-8 was observed especially by RVECs after exposure to cefuroxime or vancomycin which was exacerbated by L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP), a NOD1 ligand. Intravitreal injections in mice showed that cefuroxime and vancomycin caused retinal and vascular toxicity extending to the inner nuclear layers. Collectively, moxifloxacin causes immediate damage to retinal vascular cells in vitro, while cefuroxime and vancomycin induced significant inflammatory effects on vascular endothelial cells and caused retinal toxicity. Surgeons need to be cautious of the toxicity when antibiotics are used prophylactically especially by intravitreal administration.

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Cytotoxicity and Genotoxic Effects of Organic Extracts from Traffic-Related Particulate Matter in Human Vascular Endothelial Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.610-613.686 ◽

2012 ◽

Vol 610-613 ◽

pp. 686-690

Author(s):

Yu Shang ◽

Lan Lan Fan ◽

Ling Zhang

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Endothelial Cells ◽

Plasma Membrane ◽

Particulate Matter ◽

Vascular Endothelial Cells ◽

Membrane Damage ◽

Cell Culture Supernatant ◽

Vascular Endothelial ◽

Organic Extracts

Traffic-related particulate matter (PM) is associated with adverse cardiovascular effects. However, the direct impact of the traffic-related PM on the cytotoxicity and genotoxic damage in vascular endothelial cells is less well known. The aim of the present study is to assess whether exposure to the organic extracts of traffic related-PM (oTRP) can induce cytotoxicity, DNA damage and oxidative stress in the human umbilical vein endothelial cells (HUVEC). The cell viability was determined by MTT assay after treatment with oTRP for 24 h. The injury of the cell plasma membrane was evaluated by testing the lactate dehydrogenase (LDH) leakage in cell culture supernatant. The activity of superoxide dismutase (SOD) was determined to evaluate the level of oxidative stress in cells. DNA damage was measured by alkaline Comet assay. The results showed that significantly dose-dependent cytotoxicity and DNA damage was detected in HUVEC after treated with oTRP for 24 h. A concomitant decrease in SOD activity was observed, suggesting that oTRP may mediate genotoxic and cytotoxic effects in HUVEC through the oxidative stress pathway. These results indicate that organic extracts of traffic related-PM has a potency to cause oxidative stress, DNA damage, cell death and plasma membrane damage in HUVEC, thus may be participated in the development of cardiovascular diseases through damaging vascular endothelial cells.

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Protective Effect of Flavonoids from a Deep-Sea-Derived Arthrinium sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells

Marine Drugs ◽

10.3390/md19120712 ◽

2021 ◽

Vol 19 (12) ◽

pp. 712

Author(s):

Jia-Rong Hou ◽

Yan-Hong Wang ◽

Ying-Nan Zhong ◽

Tong-Tong Che ◽

Yang Hu ◽

...

Keyword(s):

Endothelial Cells ◽

Cardiovascular Diseases ◽

Deep Sea ◽

Nuclear Translocation ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Oxidative Injury ◽

Vascular Endothelial ◽

Level Increase ◽

Induced Apoptosis

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment.

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Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/759615 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Purum Kang ◽

Seung Ho Han ◽

Hea Kyung Moon ◽

Jeong-Min Lee ◽

Hyo-Keun Kim ◽

...

Keyword(s):

Endothelial Cells ◽

Channel Blocker ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Dependent Manner ◽

Vascular Endothelial ◽

Concentration Dependent Manner ◽

Carbonyl Cyanide ◽

Intracellular Ca ◽

Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

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Comparison of prostanoid synthesis in cultured human vascular endothelial cells derived from omentum and umbilical vein

European Journal of Vascular Surgery ◽

10.1016/s0950-821x(05)80335-4 ◽

1991 ◽

Vol 5 (5) ◽

pp. 501-506 ◽

Cited By ~ 11

Author(s):

G. Stansby ◽

N. Shukla ◽

G. Hamilton ◽

J. Jeremy

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Vascular Endothelial ◽

Prostanoid Synthesis

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Oxidized polyamines and the growth of human vascular endothelial cells. Prevention of cytotoxic effects by selective acetylation

Biochemical Journal ◽

10.1042/bj2420347 ◽

1987 ◽

Vol 242 (2) ◽

pp. 347-352 ◽

Cited By ~ 35

Author(s):

D M L Morgan

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Amine Oxidase ◽

Umbilical Vein ◽

Polyamine Oxidase ◽

Oxidation Products ◽

Vascular Endothelial ◽

Cytotoxic Effects ◽

Naturally Occurring ◽

Aminopropyl Group

The responses of human umbilical-vein vascular endothelial cells in culture to the naturally occurring polyamines spermine, spermidine and putrescine, their acetyl derivatives and oxidation products were examined. In the absence of human polyamine oxidase, exposure of cells to polyamines (up to 160 microM) had no adverse effects. In the presence of polyamine oxidase, spermine and spermidine were cytotoxic, but putrescine was not. Acetylation of the aminopropyl group of spermidine or both aminopropyl groups of spermine prevented this cytotoxicity. The amino acids corresponding to the polyamines, representing a further stage of oxidation, were also without effect. The cytotoxic effects were irreversible. Use of bovine serum amine oxidase in place of the human enzyme gave qualitatively similar results.

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Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

Cellular Physiology and Biochemistry ◽

10.1159/000487033 ◽

2018 ◽

Vol 45 (2) ◽

pp. 558-571 ◽

Cited By ~ 8

Author(s):

Yun Yi ◽

Yulin Shen ◽

Qin Wu ◽

Jingan Rao ◽

Shu Guan ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Viability ◽

Western Blotting ◽

High Glucose ◽

Vascular Endothelial Cells ◽

Control Group ◽

Vascular Endothelial ◽

A2b Receptor ◽

High Glucose Group ◽

Glucose Group

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucose-induced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A2B siRNA. The expression of the adenosine A2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

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Thrombin receptor 14-amino acid peptide binds to endothelial cells and stimulates calcium transients

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1992.263.5.l595 ◽

1992 ◽

Vol 263 (5) ◽

pp. L595-L601 ◽

Cited By ~ 4

Author(s):

C. Tiruppathi ◽

H. Lum ◽

T. T. Andersen ◽

J. W. Fenton ◽

A. B. Malik

Keyword(s):

Endothelial Cells ◽

Intracellular Calcium ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Calcium Transients ◽

Cell Protein ◽

Affinity Constant ◽

Thrombin Receptor ◽

Vascular Endothelial ◽

Amino Terminal

We examined the binding characteristics of the recently described thrombin receptor amino-terminal peptide, SFLLRNPNDKYEPF (T. K. H. Vu, D. T. Hung, V. I. Wheaton, and S. R. Coughlin. Cell 64: 1057-1068, 1991), termed TRP-14, and its effect in activating intracellular calcium transients in pulmonary vascular endothelial cells. Binding of 125I-labeled TRP-14 was found to be saturable with a affinity constant of 2 microM and maximum binding of 41 pmol/mg of cell protein. The 125I-labeled TRP-14 also interacted with bovine pulmonary microvessel endothelial cells, human umbilical vein endothelial cells, and porcine pulmonary artery smooth muscle cells. Binding of 125I-labeled diisopropylphosphoryl (DIP)-alpha-thrombin, which is catalytically inactive but binds to thrombin receptors, was not inhibited by TRP-14 or vice versa, indicating that TRP-14 did not compete for the alpha-thrombin binding site(s) on the endothelial cell surface. TRP-14 (> 1 microM) increased the concentration of intracellular calcium ([Ca2+]i) in endothelial cells with kinetics similar to the increase in [Ca2+]i triggered by alpha-thrombin. In contrast, DIP-alpha-thrombin did not increase [Ca2+]i and also did not prevent the rise in [Ca2+]i induced by the subsequent challenge with either TRP-14 or alpha-thrombin. Because the generation of TRP-14 by the proteolytically active forms of thrombin stimulated a rise in endothelial [Ca2+]i, TRP-14 may be the agonist responsible for the activation of the alpha-thrombin receptor in pulmonary vascular endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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