scholarly journals Regulation of ROS Production and Vascular Function by Carbon Monoxide

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Yoon Kyung Choi ◽  
Elaine D. Por ◽  
Young-Guen Kwon ◽  
Young-Myeong Kim
Keyword(s):  
Carbon Monoxide ◽  
Vascular Function ◽  
Biological Effects ◽  
Ros Generation ◽  
Ros Production ◽  
Cellular Mechanisms ◽  
Mitochondrial Energy Metabolism ◽  
Cellular Redox ◽  
Cellular Events ◽  
Exogenous Delivery

Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS). CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angiogenesis and mitochondrial biogenesis. Therefore, CO generated either by exogenous delivery or by HO activity can be fundamentally involved in regulating mitochondria-mediated redox cascades for adaptive gene expression and improving blood circulation (i.e., O2delivery) via neovascularization, leading to the regulation of mitochondrial energy metabolism. This paper will highlight the biological effects of CO on ROS generation and cellular redox changes involved in mitochondrial metabolism and angiogenesis. Moreover, cellular mechanisms by which CO is exploited for disease prevention and therapeutic applications will also be discussed.

Abstract P341: Osteoprotegerin-induced ROS Production and Redox Signalling is Exacerbated in Hypertension and Involves Syndecan-1 and TRPM2 Activation

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Augusto C Montezano ◽  
Ross Hepburn ◽  
Delyth Graham ◽  
Rhian M Touyz
Keyword(s):  
Vascular Function ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Vascular Dysfunction ◽  
Ros Generation ◽  
Ros Production ◽  
Redox Signalling ◽  
Wky Rats ◽  
Amplex Red ◽  
Src Activation

Osteoprotegerin (OPG) levels are increased in metabolic diseases, and are a biomarker of vascular dysfunction and cardiovascular risk. Mechanisms related to OPG-induced vascular dysfunction and its role in hypertension are not fully understood, but we previously demonstrated that OPG induces vascular dysfunction through ROS-dependent mechanisms. Here we assessed the molecular mechanisms whereby OPG regulates ROS and vascular function, with a focus on syndecan-1. VSMCs from normotensive (WKY) and hypertensive (SHRSP) rats were stimulated with OPG (50 ng/mL). ROS production was measured by lucigenin, amplex red and ELISA. In VSMCs from WKY rats, OPG increased ROS generation (158±15% vs veh, p<0.05). This effect was blocked by the syndecan-1 inhibitor (synstatin) and by removal of syndecan-1 sulfate proteoglycans side chains, chondroitinase and heparinase. OPG also increased H 2 O 2 (2 fold) and ONOO - (1.5 fold) levels in VSMCs (p<0.05). H 2 O 2 further stimulates ROS levels and redox signalling through activation of TRPM2, a redox-sensitive Ca 2+ channel. TRPM2 inhibitors, 8-bromo-ADPR (8Br) and N-(p-amylcinnamoyl)anthranilic acid (ACA), did not block OPG-induced ROS generation in VSMCs from WKY rats. Syndecan-1 activation leads to FAK and c-Src activation, which are redox-sensitive signalling proteins. FAK, but not c-Src, activation (117±2%, p<0.05) was observed after OPG stimulation of WKY VSMCs. In VSMCS from SHRSP rats, OPG effects on ROS generation were exacerbated (230±40%, p<0.05) and inhibited by synstatin, 8Br and ACA. OPG also increased FAK (118±2) and c-Src (113±1) activation (p<0.05) in VSMCs from SHRSP rats. In conclusion, OPG regulation of oxidative stress is increased in hypertension and involves not only syndecan-1, but also TRPM2 channels, which may lead to activation of redox-sensitive proteins and vascular damage.

scholarly journals ROS-induced ROS release in vascular biology: redox-redox signaling

2011 ◽  
Vol 301 (3) ◽  
pp. H647-H653 ◽  
Author(s):  
Natalya S. Zinkevich ◽  
David D. Gutterman
Keyword(s):  
Reactive Oxygen Species ◽  
Adaptive Response ◽  
Vascular Function ◽  
Common Mechanism ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Signaling Function ◽  
A Cell ◽  
Lines Of Evidence

The involvement of reactive oxygen species (ROS) in regulating vascular function both in normal vessels and as part of an adaptive response during disease has been intensively studied. From the recognition that ROS serve as important signaling molecules has emerged multiple lines of evidence that there is a functional connectivity between intracellular sites of ROS production. This cross talk has been termed ROS-induced ROS release (RIRR) and is supported by a variety of observations showing that RIRR is a common mechanism for ROS amplification and regional ROS generation. The compartmentalization of ROS production within a cell is critical to its signaling function and is facilitated by microlocalization of specific scavengers. This review will provide descriptions and examples of important mechanisms of RIRR.

Carbon monoxide activates NF-κB via ROS generation and Akt pathways to protect against cell death of hepatocytes

2008 ◽  
Vol 295 (1) ◽  
pp. G146-G152 ◽  
Author(s):  
Hoe Suk Kim ◽  
Patricia A. Loughran ◽  
Jayashree Rao ◽  
Timothy R. Billiar ◽  
Brian S. Zuckerbraun
Keyword(s):  
Carbon Monoxide ◽  
Hepatic Function ◽  
Luciferase Reporter ◽  
Ros Generation ◽  
Ros Production ◽  
Hepatocyte Apoptosis ◽  
Mobility Shift ◽  
Akt Phosphorylation ◽  
Hep3b Cells ◽  
Mobility Shift Assay

Heme oxygenase overexpression or exogenous carbon monoxide (CO) protects against hepatocyte apoptosis and fulminant hepatitis. The prevention of hepatocyte apoptosis by CO has been shown to require activation of NF-κB. The purpose of these investigations was to determine the mechanism of CO-induced hepatocyte NF-κB activation and protection against apoptosis. Primary rat or mouse hepatocytes and Hep3B cells were utilized. CO exposure was performed at 250 parts per million. Main outcome measures included cell viability, reactive oxygen species (ROS) generation, and changes in the levels of the intracellular antioxidants glutathione and ascorbate. Western blotting was performed for phospho-Akt, total Akt, and IκBα. NF-κB activation was determined by electrophoretic mobility shift assay and luciferase reporter assays. We found that CO treatment of hepatocytes prevents spontaneous apoptosis and leads to an increase in ROS production in association with Akt phosphorylation and IκB degradation. CO did not increase ROS production in respiration-deficient (ρ0) Hep3B cells. Both Akt phosphorylation and IκB degradation can be inhibited by the addition of antioxidants. Furthermore, CO-induced NF-κB activation is reversed by phosphatidylinositol 3-kinase (PI3-K) inhibitor (LY294002) or antioxidants. Additionally, prevention of spontaneous hepatocyte apoptosis by CO is reversed by PI3-K inhibition and antioxidants. In conclusion, these data implicate a survival pathway of CO-induced ROS, Akt phosphorylation, and NF-κB activation in cultured hepatocytes. This pathway may prove to be important in maintenance of hepatic function in both physiological and pathophysiological conditions.

scholarly journals Ferritinophagy-Mediated ROS Production Contributed to Proliferation Inhibition, Apoptosis, and Ferroptosis Induction in Action of Mechanism of 2-Pyridylhydrazone Dithiocarbamate Acetate

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Longlong Li ◽  
Hao Li ◽  
Yongli Li ◽  
Jiankang Feng ◽  
Deng Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Biological Effects ◽  
Underlying Mechanism ◽  
Mechanistic Study ◽  
Ros Production ◽  
Nuclear Receptor Coactivator ◽  
Cellular Events ◽  
Cycle Arrest ◽  
Underlying Mechanisms

Reactive oxygen species (ROS) production is involved in the mechanism of action of a number of drugs, but the biological effects of ROS remain to be clarified. Furthermore, ferroptosis involves iron-dependent ROS production that may be derived from ferritinophagy; however, the association between ferroptosis and ferritinophagy has not been fully established. The present study demonstrated that dithiocarbamate derivatives (iron chelators) exhibited antineoplastic properties involving ferritinophagy induction, but whether the underlying mechanisms involved ferroptosis was unknown. To gain insight into the underlying mechanism, a dithiocarbamate derivative, 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA), was prepared. An MTT assay demonstrated that PdtaA inhibited proliferation involving ROS production ( I C 50 = 23.0 ± 1.5  μM for HepG2 cells). A preliminary mechanistic study revealed that PdtaA induced both apoptosis and cell cycle arrest. Notably, PdtaA also induced ferroptosis via downregulation of GPx4 and xCT, which was first reported for a dithiocarbamate derivative. Moreover, these cellular events were associated with ROS production. To explore the origin of ROS, expression of the ferritinophagy-related genes, ferritin, and nuclear receptor coactivator (NCOA4) were measured. Immunofluorescence and western blotting analysis indicated that PdtaA-induced ferritinophagy may contribute to ROS production. To investigate the role of ferritinophagy, autophagy inhibitor 3-methyladenin or genetic knockdown of NCOA4 was employed to inhibit ferritinophagy, which significantly neutralized the action of PdtaA in both apoptosis and ferroptosis. Taken together, PdtaA-induced cell cycle arrest, apoptosis, and ferroptosis were associated with ferritinophagy.

Synthesis and Biological Activity of Embelin and its Derivatives: An Overview

2020 ◽  
Vol 20 (5) ◽  
pp. 396-407 ◽  
Author(s):  
Zhaojun Sheng ◽  
Siyuan Ge ◽  
Min Gao ◽  
Rongchao Jian ◽  
Xiaole Chen ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Effects ◽  
New Drugs ◽  
Hydroxyl Groups ◽  
Carbonyl Groups ◽  
Cellular Mechanisms ◽  
Embelia Ribes ◽  
Naturally Occurring ◽  
Ic50 Value ◽  
Apoptosis Protein

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family, and contains two carbonyl groups, a methine group and two hydroxyl groups. With embelin as the lead compound, more than one hundred derivatives have been reported. Embelin is well known for its ability to antagonize the X-linked inhibitor of apoptosis protein (XIAP) with an IC50 value of 4.1 μM. The potential of embelin and its derivatives in the treatment of various cancers has been extensively studied. In addition, these compounds display a variety of other biological effects: antimicrobial, antioxidant, analgesic, anti-inflammatory, anxiolytic and antifertility activity. This paper reviews the recent progress in the synthesis and biological activity of embelin and its derivatives. Their cellular mechanisms of action and prospects in the research and development of new drugs are also discussed.

scholarly journals Reactive Oxygen Species in Host Plant Are Required for an Early Defense Response against Attack of Stagonospora nodorum Berk. Necrotrophic Effectors SnTox

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1586
Author(s):  
Svetlana Veselova ◽  
Tatyana Nuzhnaya ◽  
Guzel Burkhanova ◽  
Sergey Rumyantsev ◽  
Igor Maksimov
Keyword(s):  
Reactive Oxygen Species ◽  
Early Stage ◽  
Reactive Oxygen ◽  
Triticum Aestivum L ◽  
Redox Status ◽  
Stagonospora Nodorum ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotrophic Effectors

Reactive oxygen species (ROS) play a central role in plant immune responses. The most important virulence factors of the Stagonospora nodorum Berk. are multiple fungal necrotrophic effectors (NEs) (SnTox) that affect the redox-status and cause necrosis and/or chlorosis in wheat lines possessing dominant susceptibility genes (Snn). However, the effect of NEs on ROS generation at the early stages of infection has not been studied. We studied the early stage of infection of various wheat genotypes with S nodorum isolates -Sn4VD, SnB, and Sn9MN, carrying a different set of NE genes. Our results indicate that all three NEs of SnToxA, SnTox1, SnTox3 significantly contributed to cause disease, and the virulence of the isolates depended on their differential expression in plants (Triticum aestivum L.). The Tsn1–SnToxA, Snn1–SnTox1and Snn3–SnTox3 interactions played an important role in inhibition ROS production at the initial stage of infection. The Snn3–SnTox3 inhibited ROS production in wheat by affecting NADPH-oxidases, peroxidases, superoxide dismutase and catalase. The Tsn1–SnToxA inhibited ROS production in wheat by affecting peroxidases and catalase. The Snn1–SnTox1 inhibited the production of ROS in wheat by mainly affecting a peroxidase. Collectively, these results show that the inverse gene-for gene interactions between effector of pathogen and product of host sensitivity gene suppress the host’s own PAMP-triggered immunity pathway, resulting in NE-triggered susceptibility (NETS). These results are fundamentally changing our understanding of the development of this economical important wheat disease.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

[PP.03.16] INCREASED ROS GENERATION INVOLVES MITOCHONDRIA IN MR-OVEREXPRESSING ADIPOCYTES – IMPACT ON VASCULAR FUNCTION.

2016 ◽  
Vol 34 ◽  
pp. e130
Author(s):  
A. Nguyen Dinh Cat ◽  
M. Friederich-Persson ◽  
M.G. Dulak-Lis ◽  
A. Sanchez ◽  
R. Nosalski ◽  
...  
Keyword(s):  
Vascular Function ◽  
Ros Generation

Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor

2013 ◽  
Vol 305 (2) ◽  
pp. H155-H162 ◽  
Author(s):  
Sayoko Ogura ◽  
Tatsuo Shimosawa ◽  
ShengYu Mu ◽  
Takashi Sonobe ◽  
Fumiko Kawakami-Mori ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ros Generation ◽  
Low Density ◽  
Ros Production ◽  
Oxidized Low Density Lipoprotein

Chronic hypoxia is one of the main causes of pulmonary hypertension (PH) associated with ROS production. Lectin-like oxidized low-density lipoprotein receptor (LOX)-1 is known to be an endothelial receptor of oxidized low-density lipoprotein, which is assumed to play a role in the initiation of ROS generation. We investigated the role of LOX-1 and ROS generation in PH and vascular remodeling in LOX-1 transgenic (TG) mice. We maintained 8- to 10-wk-old male LOX-1 TG mice and wild-type (WT) mice in normoxia (room air) or hypoxia (10% O2 chambers) for 3 wk. Right ventricular (RV) systolic pressure (RVSP) was comparable between the two groups under normoxic conditions; however, chronic hypoxia significantly increased RVSP and RV hypertrophy in LOX-1 TG mice compared with WT mice. Medial wall thickness of the pulmonary arteries was significantly greater in LOX-1 TG mice than in WT mice. Furthermore, hypoxia enhanced ROS production and nitrotyrosine expression in LOX-1 TG mice, supporting the observed pathological changes. Administration of the NADPH oxidase inhibitor apocynin caused a significant reduction in PH and vascular remodeling in LOX-1 TG mice. Our results suggest that LOX-1-ROS generation induces the development and progression of PH.

scholarly journals Hepatoprotection of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L.

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 267 ◽  
Author(s):  
Olívia R. Pereira ◽  
Rocio I. R. Macias ◽  
Maria R. M. Domingues ◽  
Jose J. G. Marin ◽  
Susana M. Cardoso
Keyword(s):  
Potassium Dichromate ◽  
Biological Effects ◽  
Antioxidant Properties ◽  
Ros Generation ◽  
Mentha Aquatica ◽  
Organic Cultivation ◽  
Chemical Models ◽  
Phenolic Components ◽  
Leonurus Cardiaca

The phenolic composition of hydroethanolic extracts of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L., obtained from plants grown under organic cultivation, was determined and their hepatoprotective effects were investigated in vitro. L. cardiaca extract was rich in phenylethenoid glycosides, especially lavandolifolioside (254 ± 36 μg/mg), whereas rosmarinic acid and eriodictyol-O-rutinoside were the major phenolic compounds of L. dentata and M. aquatica extracts, accounting for 68 ± 7 μg/mg and 145 ± 22 μg/mg, respectively. These differential phenolic components presumably account for their dissimilar antioxidant properties. While L. cardiaca extract showed moderate biological effects, M. aquatica extract displayed high antioxidant activity in chemical models, and that of L. dentata was effective in counteracting potassium dichromate-induced ROS generation in human hepatocarcinoma cells. Moreover, M. aquatica extract (50 μg/mL) and its mixture (50%/50%) with L. dentata extract displayed an effective cytoprotective effect.

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