For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
Article has an altmetric score of 4
50
references
 Top references
cited by
22
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      440
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Angiotensin II Decreases Endothelial Nitric Oxide Synthase Phosphorylation via AT 1R Nox/ROS/PP2A Pathway

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Increasing evidences suggest that angiotensin (Ang) II participates in the pathogenesis of endothelial dysfunction (ED) through multiple signaling pathways, including angiotensin type 1 receptor (AT 1R) mediated NADPH oxidase (Nox)/reactive oxygen species (ROS) signal transduction. However, the detailed mechanism is not completely understood. In this study, we reported that AngII/AT 1R-mediated activated protein phosphatase 2A (PP2A) downregulated endothelial nitric oxide synthase (eNOS) phosphorylation via Nox/ROS pathway. AngII treatment reduced the levels of phosphorylation of eNOS Ser1177 and nitric oxide (NO) content along with phosphorylation of PP2Ac (PP2A catalytic subunit) Tyr307, meanwhile increased the PP2A activity and ROS production in human umbilical vein endothelial cells (HUVECs). These changes could be impeded by AT 1R antagonist candesartan (CAN). The pretreatment of 10 −8 M PP2A inhibitor okadaic acid (OA) reversed the levels of eNOS Ser1177 and NO content. Similar effects of AngII on PP2A and eNOS were also observed in the mesenteric arteries of Sprague-Dawley rats subjected to AngII infusion via osmotic minipumps for 2 weeks. We found that the PP2A activity was increased, but the levels of PP2Ac Tyr307 and eNOS Ser1177 as well as NO content were decreased in the mesenteric arteries. The pretreatments of antioxidant N-acetylcysteine (NAC) and apocynin (APO) abolished the drop of the levels of PP2Ac Tyr307 and eNOS Ser1177 induced by AngII in HUVECs. The knockdown of p22phox by small interfering RNA (siRNA) gave rise to decrement of ROS production and increment of the levels of PP2Ac Tyr307 and eNOS Ser1177. These results indicated that AngII/AT 1R pathway activated PP2A by downregulating its catalytic subunit Tyr307 phosphorylation, which relies on the Nox activation and ROS production. In summary, our findings indicate that AngII downregulates PP2A catalytic subunit Tyr307 phosphorylation to activate PP2A via AT 1R-mediated Nox/ROS signaling pathway. The activated PP2A further decreases levels of eNOS Ser1177 phosphorylation and NO content leading to endothelial dysfunction.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Free radicals and antioxidants in normal physiological functions and human disease.

          Marian Valko, Dieter Leibfritz, Jan Moncol … (2007)
          Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
          Article 0 comments Cited 1414 times – based on 0 reviews     Review now
          Article has an altmetric score of 65
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases.

            Annalisa Natalicchio, Maria Incalza, Rossella D'Oria … (2017)
            Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between generation of reactive ROS and antioxidant defense systems represents the primary cause of endothelial dysfunction, leading to vascular damage in both metabolic and atherosclerotic diseases. Endothelial activation is the first alteration observed, and is characterized by an abnormal pro-inflammatory and pro-thrombotic phenotype of the endothelial cells lining the lumen of blood vessels. This ultimately leads to reduced nitric oxide (NO) bioavailability, impairment of the vascular tone and other endothelial phenotypic changes collectively termed endothelial dysfunction(s). This review will focus on the main mechanisms involved in the onset of endothelial dysfunction, with particular focus on inflammation and aberrant ROS production and on their relationship with classical and non-classical cardiovascular risk factors, such as hypertension, metabolic disorders, and aging. Furthermore, new mediators of vascular damage, such as microRNAs, will be discussed. Understanding mechanisms underlying the development of endothelial dysfunction is an important base of knowledge to prevent vascular damage in metabolic and cardiovascular diseases.
            Article 0 comments Cited 375 times – based on 0 reviews     Review now
            Article has an altmetric score of 4
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              NADPH oxidases: an overview from structure to innate immunity-associated pathologies.

              Arvind Panday, Malaya Sahoo, Diana Benito Osorio … (2015)
              Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), play important roles in immunity, cell growth, and cell signaling. In excess, however, ROS are lethal to cells, and the overproduction of these molecules leads to a myriad of devastating diseases. The key producers of ROS in many cells are the NOX family of NADPH oxidases, of which there are seven members, with various tissue distributions and activation mechanisms. NADPH oxidase is a multisubunit enzyme comprising membrane and cytosolic components, which actively communicate during the host responses to a wide variety of stimuli, including viral and bacterial infections. This enzymatic complex has been implicated in many functions ranging from host defense to cellular signaling and the regulation of gene expression. NOX deficiency might lead to immunosuppression, while the intracellular accumulation of ROS results in the inhibition of viral propagation and apoptosis. However, excess ROS production causes cellular stress, leading to various lethal diseases, including autoimmune diseases and cancer. During the later stages of injury, NOX promotes tissue repair through the induction of angiogenesis and cell proliferation. Therefore, a complete understanding of the function of NOX is important to direct the role of this enzyme towards host defense and tissue repair or increase resistance to stress in a timely and disease-specific manner.
              Article 0 comments Cited 281 times – based on 0 reviews     Review now
              Article has an altmetric score of 23
                Bookmark
                All references

                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Physiol
                Journal ID (iso-abbrev): Front Physiol
                Journal ID (publisher-id): Front. Physiol.
                Title: Frontiers in Physiology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-042X
                Publication date (Electronic): 30 September 2020
                Publication date Collection: 2020
                Volume: 11
                Electronic Location Identifier: 566410
                Affiliations
                [1] 1Department of Pathophysiology, Guizhou Medical University , Guiyang, China
                [2] 2Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University , Guiyang, China
                [3] 3Department of Pathology, The Second Clinical Medical School of Inner Mongolia University for the Nationalities , Yakeshi, China
                [4] 4Department of Cardiology, The Second Provincial People’s Hospital of Gansu , Lanzhou, China
                [5] 5Department of Cardiology, Affiliated Hospital of Guizhou Medical University , Guiyang, China
                [6] 6Department of Neurology, Affiliated Hospital of Guizhou Medical University , Guiyang, China
                [7] 7Key Laboratory of Medical Molecular Biology, Guizhou Medical University , Guiyang, China
                [8] 8Davis Heart and Lung Research Institute, The Ohio State University College of Medicine , Columbus, OH, United States
                Author notes

                Edited by: Jun Ren, University of Washington, United States

                Reviewed by: Si Jin, Huazhong University of Science and Technology, China; Thiago Bruder Do Nascimento, University of Pittsburgh, United States

                *Correspondence: Deqin Lu, dqlu91@ 123456hotmail.com

                †These authors have contributed equally to this work

                This article was submitted to Vascular Physiology, a section of the journal Frontiers in Physiology

                Article
                DOI: 10.3389/fphys.2020.566410
                PMC ID: 7580705
                PubMed ID: 33162896
                SO-VID: 92ba4503-161b-4846-892a-7e8e4a1069c9
                Copyright © Copyright © 2020 Ding, Yu, Jiang, Luo, Zhang, Wang, Yang, Wang, Wang, Zhuang, Wu, Zhang, Xia and Lu.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 03 June 2020
                Date accepted : 08 September 2020
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 50, Pages: 12, Words: 7616
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 30871003
                Award ID: 31460267
                Funded by: Key Social Development Project of Guizhou Provincial Science and Technology Department
                Funded by: the Cooperation Project of Guizhou Provincial Science and Technology Department
                Funded by: Guizhou Medical University 10.13039/501100010265
                Funded by: ADA grant
                Award ID: 1-19-IBS-142
                Categories
                Subject: Physiology
                Subject: Original Research

                ScienceOpen disciplines: Anatomy & Physiology
                Keywords: angiotensin ii,angiotensin ii type 1 receptor,protein phosphatase 2a,endothelial nitric oxide synthase,nadph oxidase
                Data availability:
                ScienceOpen disciplines: Anatomy & Physiology
                Keywords: angiotensin ii, angiotensin ii type 1 receptor, protein phosphatase 2a, endothelial nitric oxide synthase, nadph oxidase

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content440

                See all similar

                Cited by21

                See all cited by

                Most referenced authors853

                See all reference authors