HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells

2006 ◽  
Vol 291 (5) ◽  
pp. C897-C908 ◽  
Author(s):  
Shyamali Basuroy ◽  
Sujoy Bhattacharya ◽  
Dilyara Tcheranova ◽  
Yan Qu ◽  
Raymond F. Regan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Serum Deprivation ◽  
Oxygen Species ◽  
Tnf Α ◽  
Endogenous Protection ◽  
Cerebral Vascular

Tumor necrosis factor-α (TNF-α) causes oxidative stress and apoptosis in a variety of cell types. Heme oxygenase (HO) degrades heme to bilirubin, an antioxidant, and carbon monoxide (CO), a cell cycle modulator, and a vasodilator. Newborn pig cerebral microvascular endothelial cells (CMVEC) highly express constitutive HO-2. We investigated the role of HO-2 in protection against TNF-α-induced apoptosis in cerebral vascular endothelium. In CMVEC from mice and newborn pigs, 15 ng/ml TNF-α alone, or with 10 μg/ml cycloheximide (CHX) caused apoptosis detected by nuclear translocation of p65 NF-κB, caspase-3 activation, DNA fragmentation, cell-cell contact destabilization, and cell detachment. TNF-α did not induce HO-1 expression in CMVEC. CMVEC from HO-2 knockout mice showed greater sensitivity to apoptosis caused by serum deprivation and TNF-α than did wild-type mice. TNF-α increased reactive oxygen species generation, including hydrogen peroxide and superoxide radicals, as detected by dihydrorhodamine-123 and dihydroethidium. The TNF-α response was inhibited by superoxide dismutase and catalase suggesting apoptosis is oxidative stress related. Inhibition of endogenous HO-2 in newborn pig CMVEC increased oxidative stress and exaggerated apoptosis caused by serum deprivation and TNF-α. In HO-1-overexpressing CMVEC (HO-1 selective induction by cobalt portophyrin), TNF-α did not cause apoptosis. A CO-releasing compound, CORM-A1, and bilirubin blocked TNF-α-induced reactive oxygen species accumulation and apoptosis consistent with the antioxidant and antiapoptotic roles of the end products of HO activity. We conclude that HO-2 is critical for protection of cerebrovascular endothelium against apoptotic changes induced by oxidative stress and cytokine-mediated inflammation.

Activation of NF-κB induced by H2O2 and TNF-α and its effects on ICAM-1 expression in endothelial cells

2000 ◽  
Vol 279 (2) ◽  
pp. L302-L311 ◽  
Author(s):  
Andrea L. True ◽  
Arshad Rahman ◽  
Asrar B. Malik
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Nuclear Dna ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Intercellular Adhesion Molecule ◽  
Oxygen Species ◽  
Tnf Α

Reactive oxygen species have been proposed to signal the activation of the transcription factor nuclear factor (NF)-κB in response to tumor necrosis factor (TNF)-α challenge. In the present study, we investigated the effects of H2O2 and TNF-α in mediating activation of NF-κB and transcription of the intercellular adhesion molecule (ICAM)-1 gene. Northern blot analysis showed that TNF-α exposure of human dermal microvascular endothelial cells (HMEC-1) induced marked increases in ICAM-1 mRNA and cell surface protein expression. In contrast, H2O2 added at subcytolytic concentrations failed to activate ICAM-1 expression. Challenge with H2O2 also failed to induce NF-κB-driven reporter gene expression in the transduced HMEC-1 cells, whereas TNF-α increased the NF-κB-driven gene expression ∼10-fold. Gel supershift assay revealed the presence of p65 (Rel A), p50, and c-Rel in both H2O2- and TNF-α-induced NF-κB complexes bound to the ICAM-1 promoter, with the binding of the p65 subunit being the most prominent. In vivo phosphorylation studies, however, showed that TNF-α exposure induced marked phosphorylation of NF-κB p65 in HMEC-1 cells, whereas H2O2 had no effect. These results suggest that reactive oxygen species generation in endothelial cells mediates the binding of NF-κB to nuclear DNA, whereas TNF-α generates additional signals that induce phosphorylation of the bound NF-κB p65 and confer transcriptional competency to NF-κB.

Toxicity assessment of metallic nickel nanoparticles in various biological models: An interplay of reactive oxygen species, oxidative stress, and apoptosis

2021 ◽  
pp. 074823372110110
Author(s):  
Shabnoor Iqbal ◽  
Farhat Jabeen ◽  
Abdul Shakoor Chaudhry ◽  
Muhammad Ajmal Shah ◽  
Gaber El-Saber Batiha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nickel Nanoparticles ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Volume Ratio ◽  
Nuclear Factor Κb ◽  
Metallic Nickel ◽  
Oxygen Species

Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is detrimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world applications. This review mainly focuses on the notable pathophysiological activities of Ni-NPs in various research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads to the upregulation of nuclear factor-κB and promotes further signaling cascades. Ni-NPs may contribute to provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1α and mitogen-activated protein kinases pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK, p-ERK1/2, interleukin (IL)-3, TNF-α, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9. Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.

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 Comparison of Efficacies of Different Jakyakgamcho-tang Extracts on H2O2-Induced C2C12 Cell Viability

2020 ◽  
Author(s):  
Young Sook Kim ◽  
Heung Joo Yuk ◽  
Dong-Seon Kim
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Muscle Pain ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ethanol Extract ◽  
Oxygen Species ◽  
Water Extracts ◽  
Ethanol Extracts

Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang has been used in traditional Eastern medicine to treat muscle pain. Here, we compared various solvent-based Jakyakgamcho-tang extracts in terms of their effects against hydrogen peroxide-induced oxidative stress in murine C2C12 skeletal muscle cells. Total phenolic content and total flavonoid content in 30% ethanol extracts of Jakyakgamcho-tang were higher than those of water extracts of Jakyakgamcho-tang. Ethanol extracts of Jakyakgamcho-tang had stronger antioxidant and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and 2,2´-diphenyl-1-picrylhydrazyl-scavenging activity than water extracts of Jakyakgamcho-tang. The ethanol extract of Jakyakgamcho-tang inhibited peroxide-induced cell viability and intracellular reactive oxygen species generation more effectively than the water extract of Jakyakgamcho-tang in a dose-dependent manner. These results suggest that the ethanol extract of Jakyakgamcho-tang is relatively more efficacious at protecting against oxidative stress-induced muscle cell death because it prevents reactive oxygen species generation in C2C12 cells. Moreover, the current study indicated that the effective dose of the ethanol extract of Jakyakgamcho-tang required to alleviate muscle pain might be lower than that required for Jakyakgamcho-tang.

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.

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: A novel antioxidative mechanism

2007 ◽  
Vol 97 (01) ◽  
pp. 88-98 ◽  
Author(s):  
Christina Barja-Fidalgo ◽  
Vany Nascimento-Silva ◽  
Maria Arruda ◽  
Iolanda Fierro
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Ros Generation ◽  
Oxygen Species ◽  
Lipoxin A4 ◽  
Pre Treatment

SummaryLipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A4 analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1–100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47phox to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF-κB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

scholarly journals LPS from P. gingivalis Negatively Alters Gingival Cell Mitochondrial Bioenergetics

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kiran Napa ◽  
Andrea C. Baeder ◽  
Jeffrey E. Witt ◽  
Sarah T. Rayburn ◽  
Madison G. Miller ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Function ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Human Gingival Fibroblast ◽  
Gingival Fibroblast ◽  
Oxygen Species ◽  
Atp Production ◽  
Lps Treatment

Objective. Oral inflammatory pathologies are linked to increased oxidative stress, thereby partly explaining their relevance in the etiology of systemic disorders. The purpose of this work was to determine the degree to which LPS from Porphyromonas gingivalis, the primary pathogen related to oral inflammation, altered gingival mitochondrial function and reactive oxygen species generation. Methods. Human gingival fibroblast (HGF-1) cells were treated with lipopolysaccharide of P. gingivalis. Mitochondrial function was determined via high-resolution respirometry. Results. LPS-treated HGF-1 cells had significantly higher mitochondrial complex IV and higher rates of mitochondrial respiration. However, this failed to translate into greater ATP production, as ATP production was paradoxically diminished with LPS treatment. Nevertheless, production of the reactive H2O2 was elevated with LPS treatment. Conclusions. LPS elicits an increase in gingival cell mitochondria content, with a subsequent increase in reactive oxygen species production (i.e., H2O2), despite a paradoxical reduction in ATP generation. These findings provide an insight into the nature of oxidative stress in oral inflammatory pathologies.

scholarly journals Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

2009 ◽  
Vol 11 (4) ◽  
pp. 747-764 ◽  
Author(s):  
Srikanth Pendyala ◽  
Irina A Gorshkova ◽  
Peter V. Usatyuk ◽  
Donghong He ◽  
Arjun Pennathur ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Human Lung ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Lung Endothelial Cells ◽  
And Migration

scholarly journals Kallistatin attenuates endothelial apoptosis through inhibition of oxidative stress and activation of Akt-eNOS signaling

2010 ◽  
Vol 299 (5) ◽  
pp. H1419-H1427 ◽  
Author(s):  
Bo Shen ◽  
Lin Gao ◽  
Yi-Te Hsu ◽  
Grant Bledsoe ◽  
Makato Hagiwara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Oxygen Species ◽  
Phosphatidylinositol 3 Kinase ◽  
Reactive Oxygen Species Formation ◽  
Endothelial Apoptosis ◽  
Species Formation ◽  
Tnf Α

Kallistatin is a regulator of vascular homeostasis capable of controlling a wide spectrum of biological actions in the cardiovascular and renal systems. We previously reported that kallistatin inhibited intracellular reactive oxygen species formation in cultured cardiac and renal cells. The present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced vascular injury and endothelial cell apoptosis. We found that kallistatin gene delivery significantly attenuated aortic superoxide formation and glomerular capillary loss in hypertensive DOCA-salt rats. In cultured endothelial cells, kallistatin suppressed TNF-α-induced cellular apoptosis, and the effect was blocked by the pharmacological inhibition of phosphatidylinositol 3-kinase and nitric oxide synthase (NOS) and by the knockdown of endothelial NOS (eNOS) expression. The transduction of endothelial cells with adenovirus expressing dominant-negative Akt abolished the protective effect of kallistatin on endothelial apoptosis and caspase activity. In addition, kallistatin inhibited TNF-α-induced reactive oxygen species formation and NADPH oxidase activity, and these effects were attenuated by phosphatidylinositol 3-kinase and NOS inhibition. Kallistatin also prevented the induction of Bim protein and mRNA expression by oxidative stress. Moreover, the downregulation of forkhead box O 1 (FOXO1) and Bim expression suppressed TNF-α-mediated endothelial cell death. Furthermore, the antiapoptotic actions of kallistatin were accompanied by Akt-mediated FOXO1 and eNOS phosphorylation, as well as increased NOS activity. These findings indicate a novel role of kallistatin in the protection against vascular injury and oxidative stress-induced endothelial apoptosis via the activation of Akt-dependent eNOS signaling.

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