scholarly journals Ginsenoside Rb1 Blocks Ritonavir-Induced Oxidative Stress and eNOS Downregulation through Activation of Estrogen Receptor-Beta and Upregulation of SOD in Human Endothelial Cells

2019 ◽  
Vol 20 (2) ◽  
pp. 294 ◽  
Author(s):  
Jian-Ming Lü ◽  
Jun Jiang ◽  
Md Jamaluddin ◽  
Zhengdong Liang ◽  
Qizhi Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Estrogen Receptor Beta ◽  
Luciferase Reporter ◽  
Oxygen Species ◽  
Ginsenoside Rb1 ◽  
Human Endothelial Cells ◽  
Highly Active ◽  
Low Levels ◽  
Receptor Beta

We have previously shown that ritonavir (RTV), a highly active anti-retroviral therapy (HAART) drug, can cause endothelial dysfunction through oxidative stress. Several antioxidants including ginsenoside Rb1, a compound with antioxidant effect, can effectively block this side effect of RTV in endothelial cells. In the current study, we explored a mechanism by which ginsenoside Rb1 could protect these cells via binding of estrogen receptors (ERs). We found that several human endothelial cell lines differentially expressed ER-β and had very low levels of ER-α. RTV treatment significantly increased the production of reactive oxygen species (ROS) and decreased the expression of endothelial nitric oxidase synthase (eNOS) and superoxide dismutase (SOD) in HUVECs, while Rb1 effectively blocked these effects of RTV. These effects of Rb1 were effectively inhibited by silencing ER-β, indicating that ginsenoside Rb1 requires ER-β for its antioxidant activity in inhibiting the deleterious effect of RTV in human endothelial cells. Furthermore, Rb1 specifically activated ER-β transactivation activity by ER-β luciferase reporter assay. Rb1 competitively bound to ER-β, which was determined by the high sensitive fluorescent polarization assay.

Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress

2001 ◽  
Vol 59 (s78) ◽  
pp. 120-123 ◽  
Author(s):  
Jan Galle ◽  
Alexandra Heinloth ◽  
Christoph Wanner ◽  
Kathrin Heermeier
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Human Endothelial Cells ◽  
Dual Effect

Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection

2006 ◽  
Vol 290 (5) ◽  
pp. C1399-C1410 ◽  
Author(s):  
Helena Parfenova ◽  
Shyamali Basuroy ◽  
Sujoy Bhattacharya ◽  
Dilyara Tcheranova ◽  
Yan Qu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Vascular Endothelium ◽  
Vascular Endothelial Cells ◽  
Glutamate Toxicity ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
Apoptotic Effects ◽  
Cerebral Vascular

In cerebral circulation, epileptic seizures associated with excessive release of the excitatory neurotransmitter glutamate cause endothelial injury. Heme oxygenase (HO), which metabolizes heme to a vasodilator, carbon monoxide (CO), and antioxidants, biliverdin/bilirubin, is highly expressed in cerebral microvessels as a constitutive isoform, HO-2, whereas the inducible form, HO-1, is not detectable. Using cerebral vascular endothelial cells from newborn pigs and HO-2-knockout mice, we addressed the hypotheses that 1) glutamate induces oxidative stress-related endothelial death by apoptosis, and 2) HO-1 and HO-2 are protective against glutamate cytotoxicity. In cerebral endothelial cells, glutamate (0.1–2.0 mM) increased formation of reactive oxygen species, including superoxide radicals, and induced major keystone events of apoptosis, such as NF-κB nuclear translocation, caspase-3 activation, DNA fragmentation, and cell detachment. Glutamate-induced apoptosis was greatly exacerbated in HO-2 gene-deleted murine cerebrovascular endothelial cells and in porcine cells with pharmacologically inhibited HO-2 activity. Glutamate toxicity was prevented by superoxide dismutase, suggesting apoptotic changes are oxidative stress related. When HO-1 was pharmacologically upregulated by cobalt protoporphyrin, apoptotic effects of glutamate in cerebral endothelial cells were completely prevented. Glutamate-induced reactive oxygen species production and apoptosis were blocked by a CO-releasing compound, CORM-A1 (50 μM), and by bilirubin (1 μM), consistent with the antioxidant and cytoprotective roles of the end products of HO activity. We conclude that both HO-1 and HO-2 have anti-apoptotic effects against oxidative stress-related glutamate toxicity in cerebral vascular endothelium. Although HO-1, when induced, provides powerful protection, HO-2 is an essential endogenous anti-apoptotic factor against glutamate toxicity in the cerebral vascular endothelium.

scholarly journals Cytoprotection of human endothelial cells from oxidative stress by polyphenols: the role of gene expression versus direct antioxidant effect

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Xinyu Wang ◽  
James Bynum ◽  
Salomon Stavchansky ◽  
Michael Dubick ◽  
Robert Hackman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Endothelial Cells ◽  
Antioxidant Effect ◽  
Human Endothelial Cells

scholarly journals LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

APOPTOSIS ◽  
2014 ◽  
Vol 19 (5) ◽  
pp. 776-788 ◽  
Author(s):  
James L. Figarola ◽  
Jyotsana Singhal ◽  
Samuel Rahbar ◽  
Sanjay Awasthi ◽  
Sharad S. Singhal
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Human Endothelial Cells

Oxidative stress and apoptosis are induced in human endothelial cells exposed to urban particulate matter

2010 ◽  
Vol 24 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Angélica Montiel-Dávalos ◽  
María de Jesús Ibarra-Sánchez ◽  
José Luis Ventura-Gallegos ◽  
Ernesto Alfaro-Moreno ◽  
Rebeca López-Marure
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Particulate Matter ◽  
Human Endothelial Cells ◽  
Urban Particulate Matter

Detection of oxidative stress induced by calcium phosphate bions in human arterial endothelial cells

2021 ◽  
pp. 70-78
Author(s):  
А.Г. Кутихин ◽  
Д.К. Шишкова ◽  
Р.А. Мухамадияров ◽  
Е.А. Великанова
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cell Death ◽  
Superoxide Dismutase ◽  
Calcium Phosphate ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bafilomycin A1 ◽  
Arterial Endothelial Cells

Введение. Кальций-фосфатные бионы (КФБ) формируются в организме человека при перенасыщении сыворотки ионами кальция и фосфора и вызывают дисфункцию эндотелия, однако молекулярные механизмы нарушения функционирования эндотелия при воздействии КФБ не ясны. Цель исследования - выяснение роли кальций-фосфатных бионов различной формы в развитии окислительного стресса в артериальных эндотелиальных клетках (ЭК) человека. Методика. Для детекции окислительного стресса к конфлюэнтным культурам первичных ЭК коронарной и внутренней грудной артерии человека добавляли равные концентрации КФБ сферической или игольчатой формы (СКФБ и ИКФБ соответственно) с последующим культивированием в течение 1 и 4 ч, добавлением флюоресцентных индикаторов окислительного стресса MitoSOX Red и CellROX Green и конфокальной микроскопией. Измеряли концентрацию продуктов перекисного окисления липидов в культуральной жидкости через 24 ч экспозиции эндотелиальных клеток КФБ. Анализ нейтрализации цитотоксических эффектов перекисного окисления липидов проводили путем добавления к ЭК супероксиддисмутазы и каталазы на 4 или 24 ч (одновременно с КФБ). Для сравнения механизмов клеточной гибели при воздействии СКФБ и ИКФБ анализировали цитотоксичность обоих типов бионов при одновременном воздействии лизосомального ингибитора бафиломицина А1. Результаты. Значимого увеличения генерации активных форм кислорода (АФК) в результате экспозиции СКФБ (независимо от линии ЭК и продолжительности экспозиции) не было выявлено. В то же время наблюдалось повышение генерации супероксида через 4 ч, а иных свободных радикалов через 1 ч после добавления ИКФБ к ЭК. Предварительная нейтрализация АФК супероксиддисмутазой и каталазой частично защищала ЭК от индуцируемой ИКФБ гибели. При этом добавление бафиломицина А1 к ЭК частично защищало их от гибели только при воздействии СКФБ, но не ИКФБ. Заключение. Гибель ЭК при воздействии СКФБ происходит в результате первичного повреждения лизосом, а при воздействии ИКФБ - в первую очередь вследствие окислительного стресса. Background. Calcium phosphate bions (CPB) form in the human blood upon its supersaturation with calcium and phosphate and provoke endothelial dysfunction; however, the molecular mechanisms of these pathological processes remain unclear. Aim. To elucidate the role of differently shaped CPBs in induction of oxidative stress in human arterial endothelial cells (Ecs). Methods. For detection of oxidative stress, equal concentrations of spherical CPB (CPB-S) or needle-shaped CPB (CPB-N) were added to confluent cultures of primary human coronary artery and internal thoracic artery ECs for 1 and 4 h; this was followed by MitoSOX Red and CellROX Green staining and subsequent confocal microscopy. Concentration of thiobarbituric acid-reactive substances was measured in the EC culture supernatant at 24 h of the CPB exposure. The lipid peroxidation cytotoxicity was neutralized by adding superoxide dismutase and catalase to ECs for 4 or 24 h. To compare cell death subroutines induced by CPB-S and CPB-N, the effect of bafilomycin A1, a lysosomal inhibitor, on CRB cytotoxicity was studied. Results. No increase in reactive oxygen species generation was observed in the CPB-S exposure, regardless of the EC line and exposure duration. However, addition of CPB-N to ECs increased the production of superoxide and other free radicals after four- and one-hour exposure, respectively. Prior neutralization of reactive oxygen species with superoxide dismutase and catalase partially protected ECs from CPB-N- but not CPB-S-induced death while bafilomycin A1, vice versa, protected ECs from CPB-S- but not CPB-N-induced death. Conclusion. CPB-S cause cell death due to primary damage of lysosomes whereas CPB-N induce apoptosis due to oxidative stress.

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