LIVIVO - Search results -

Search results

Result 1 - 10 of total 16

Search options

Article: Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance.

Corsello, Tiziana / Komaravelli, Narayana / Casola, Antonella

2018 Volume 7, Issue 10

Abstract: Hydrogen sulfide (H₂S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response. Three enzymes mediate the endogenous ... ...

Abstract	Hydrogen sulfide (H₂S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response. Three enzymes mediate the endogenous production of H₂S: cystathione β-synthase (
Language	English
Publishing date	2018-09-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox7100129
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses.

Komaravelli, Narayana / Casola, Antonella

Journal of pharmacogenomics & pharmacoproteomics

2014 Volume 5, Issue 4

Abstract: Reactive oxygen species (ROS) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. Low levels of ROS are involved in cellular signaling and are well controlled by the cellular ...

Abstract	Reactive oxygen species (ROS) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. Low levels of ROS are involved in cellular signaling and are well controlled by the cellular antioxidant defense system. Elevated levels of ROS generation due to pollutants, toxins and radiation exposure, as well as infections, are associated with oxidative stress causing cellular damage. Several respiratory viruses, including respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza, induce increased ROS formation, both intracellularly and as a result of increased inflammatory cell recruitment at the site of infection. They also reduce antioxidant enzyme (AOE) levels and/or activity, leading to unbalanced oxidative-antioxidant status and subsequent oxidative cell damage. Expression of several AOE is controlled by the activation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2), through binding to the antioxidant responsive element (ARE) present in the AOE gene promoters. While exposure to several pro-oxidant stimuli usually leads to Nrf2 activation and upregulation of AOE expression, respiratory viral infections are associated with inhibition of AOE expression/activity, which in the case of RSV and hMPV is associated with reduced Nrf2 nuclear localization, decreased cellular levels and reduced ARE-dependent gene transcription. Therefore, administration of antioxidant mimetics or Nrf2 inducers represents potential viable therapeutic approaches to viral-induced diseases, such as respiratory infections and other infections associated with decreased cellular antioxidant capacity.
Language	English
Publishing date	2014-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2710924-0
ISSN	2153-0645
ISSN	2153-0645
DOI	10.4172/2153-0645.1000141
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.

Zhao, Yanhua / Chahar, Harendra Singh / Komaravelli, Narayana / Dossumbekova, Anar / Casola, Antonella

Virology

2019 Volume 531, Page(s) 183–191

Abstract: Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals. Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of ... ...

Abstract	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals. Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism. We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways. On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished. Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
MeSH term(s)	Cell Line ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Glycolysis ; Hexosamines/biosynthesis ; Humans ; Metabolic Networks and Pathways ; Metapneumovirus/genetics ; Metapneumovirus/physiology ; Oxidative Phosphorylation ; Paramyxoviridae Infections/genetics ; Paramyxoviridae Infections/metabolism ; Paramyxoviridae Infections/physiopathology ; Paramyxoviridae Infections/virology ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/virology ; Virus Replication
Chemical Substances	Hexosamines
Language	English
Publishing date	2019-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2019.03.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.172: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein - ring finger protein 4 dependent pathway.

Komaravelli, Narayana / Ansar, Maria / Garofalo, Roberto P / Casola, Antonella

Free radical biology & medicine

2017 Volume 113, Page(s) 494–504

Abstract: Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular ... ...

Abstract	Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway. Although degradation via KEAP1 is the most common mechanism, silencing KEAP1 expression did not rescue NRF2 levels during RSV infection. We found that RSV-induced NRF2 degradation occurs in an SUMO-specific E3 ubiquitin ligase - RING finger protein 4 (RNF4)-dependent manner. NRF2 is progressively SUMOylated in RSV infection and either blocking SUMOylation or silencing RNF4 expression rescued both NRF2 nuclear levels and transcriptional activity. RNF4 associates with promyelocytic leukemia - nuclear bodies (PML-NBs). RSV infection induces the expression of PML and PML-NBs formation in an interferon (INF)-dependent manner and also induces NRF2 - PMN-NBs association. Inhibition of PML-NB formation by blocking IFN pathway or silencing PML expression resulted in a significant reduction of RSV-associated NRF2 degradation and increased antioxidant enzyme expression, identifying the RNF4-PML pathway as a key regulator of antioxidant defenses in the course of viral infection.
MeSH term(s)	A549 Cells ; Cell Line, Tumor ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors ; Kelch-Like ECH-Associated Protein 1/genetics ; Kelch-Like ECH-Associated Protein 1/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Oxidative Stress ; Promyelocytic Leukemia Protein/antagonists & inhibitors ; Promyelocytic Leukemia Protein/genetics ; Promyelocytic Leukemia Protein/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; Respiratory Syncytial Viruses/genetics ; Respiratory Syncytial Viruses/growth & development ; Respiratory Syncytial Viruses/metabolism ; Signal Transduction ; Small Ubiquitin-Related Modifier Proteins/antagonists & inhibitors ; Small Ubiquitin-Related Modifier Proteins/genetics ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Ubiquitination ; Ubiquitins/antagonists & inhibitors ; Ubiquitins/genetics ; Ubiquitins/metabolism
Chemical Substances	KEAP1 protein, human ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; RNA, Small Interfering ; RNF4 protein, human ; Reactive Oxygen Species ; SUMO2 protein, human ; SUMO3 protein, human ; Small Ubiquitin-Related Modifier Proteins ; Transcription Factors ; Ubiquitins ; PML protein, human (143220-95-5) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2017-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2017.10.380
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2109: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Respiratory Syncytial Virus Infection Changes Cargo Composition of Exosome Released from Airway Epithelial Cells.

Chahar, Harendra Singh / Corsello, Tiziana / Kudlicki, Andrzej S / Komaravelli, Narayana / Casola, Antonella

Scientific reports

2018 Volume 8, Issue 1, Page(s) 387

Abstract: Exosomes are microvesicles known to carry biologically active molecules, including RNA, DNA and proteins. Viral infections can induce profound changes in exosome composition, and exosomes have been implicated in viral transmission and pathogenesis. No ... ...

Abstract	Exosomes are microvesicles known to carry biologically active molecules, including RNA, DNA and proteins. Viral infections can induce profound changes in exosome composition, and exosomes have been implicated in viral transmission and pathogenesis. No information is current available regarding exosome composition and function during infection with Respiratory Syncytial Virus (RSV), the most important cause of lower respiratory tract infections in children. In this study, we characterized exosomes released from RSV-infected lung carcinoma-derived A549 cells. RNA deep sequencing revealed that RSV exosomes contain a diverse range of RNA species like messenger and ribosomal RNA fragments, as well as small noncoding RNAs, in a proportion different from exosomes isolated from mock-infected cells. We observed that both RNA and protein signatures of RSV were present in exosomes, however, they were not able to establish productive infection in uninfected cells. Exosomes isolated from RSV-infected cells were able to activate innate immune response by inducing cytokine and chemokine release from human monocytes and airway epithelial cells. These data suggest that exosomes may play an important role in pathogenesis or protection against disease, therefore understating their role in RSV infection may open new avenues for target identification and development of novel therapeutics.
MeSH term(s)	A549 Cells ; Cells, Cultured ; Cytokines/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/immunology ; Exosomes/genetics ; Exosomes/immunology ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunity, Innate ; Models, Biological ; Respiratory Syncytial Virus Infections/genetics ; Respiratory Syncytial Virus Infections/immunology ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Virus, Human/genetics ; Respiratory Syncytial Virus, Human/immunology ; Respiratory System/cytology ; Respiratory System/immunology ; Sequence Analysis, RNA/methods
Chemical Substances	Cytokines
Language	English
Publishing date	2018-01-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-18672-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Role of dietary antioxidants in human metapneumovirus infection

Komaravelli, Narayana / Kelley, John P / Garofalo, Matteo P / Wu, Haotian / Casola, Antonella / Kolli, Deepthi

Virus research. 2015 Mar. 16, v. 200

2015

Abstract: Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important ... ...

Abstract	Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.
Keywords	Human metapneumovirus ; antioxidants ; children ; elderly ; epithelial cells ; genes ; immunocompromised population ; inflammation ; interferon regulatory factors ; lungs ; oxidative stress ; promoter regions ; protective effect ; protein synthesis ; quercetin ; respiratory tract diseases ; resveratrol ; secretion ; transcription (genetics) ; virus assembly
Language	English
Dates of publication	2015-0316
Size	p. 19-23.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2015.01.018
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 1965: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Role of dietary antioxidants in human metapneumovirus infection.

Komaravelli, Narayana / Kelley, John P / Garofalo, Matteo P / Wu, Haotian / Casola, Antonella / Kolli, Deepthi

Virus research

2015 Volume 200, Page(s) 19–23

Abstract	Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.
MeSH term(s)	Antioxidants/pharmacology ; Cell Line ; Cytokines/genetics ; Cytokines/immunology ; Dietary Supplements/analysis ; Humans ; Metapneumovirus/drug effects ; Metapneumovirus/genetics ; Metapneumovirus/physiology ; Oxidative Stress/drug effects ; Paramyxoviridae Infections/drug therapy ; Paramyxoviridae Infections/immunology ; Paramyxoviridae Infections/metabolism ; Paramyxoviridae Infections/virology ; Quercetin/pharmacology ; Stilbenes/pharmacology ; Virus Replication/drug effects
Chemical Substances	Antioxidants ; Cytokines ; Stilbenes ; Quercetin (9IKM0I5T1E) ; resveratrol (Q369O8926L)
Language	English
Publishing date	2015-03-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2015.01.018
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 1965: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Interplay between MEK-ERK signaling, cyclin D1, and cyclin-dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons.

Modi, Prashant Kumar / Komaravelli, Narayana / Singh, Neha / Sharma, Pushkar

Molecular biology of the cell

2012 Volume 23, Issue 18, Page(s) 3722–3730

Abstract: In response to neurotoxic signals, postmitotic neurons make attempts to reenter the cell cycle, which results in their death. Although several cell cycle proteins have been implicated in cell cycle-related neuronal apoptosis (CRNA), the molecular ... ...

Abstract	In response to neurotoxic signals, postmitotic neurons make attempts to reenter the cell cycle, which results in their death. Although several cell cycle proteins have been implicated in cell cycle-related neuronal apoptosis (CRNA), the molecular mechanisms that underlie this important event are poorly understood. Here, we demonstrate that neurotoxic agents such as β-amyloid peptide cause aberrant activation of mitogen-activated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling, which promotes the entry of neurons into the cell cycle, resulting in their apoptosis. The MEK-ERK pathway regulates CRNA by elevating the levels of cyclin D1. The increase in cyclin D1 attenuates the activation of cyclin-dependent kinase 5 (cdk5) by its neuronal activator p35. The inhibition of p35-cdk5 activity results in enhanced MEK-ERK signaling, leading to CRNA. These studies highlight how neurotoxic signals reprogram and alter the neuronal signaling machinery to promote their entry into the cell cycle, which eventually leads to neuronal cell death.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Amyloid beta-Peptides/pharmacology ; Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Apoptosis/physiology ; Blotting, Western ; Butadienes/pharmacology ; Cell Cycle/drug effects ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cells, Cultured ; Cyclin D1/genetics ; Cyclin D1/metabolism ; Cyclin-Dependent Kinase 5/genetics ; Cyclin-Dependent Kinase 5/metabolism ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases/metabolism ; HEK293 Cells ; Humans ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/genetics ; MAP Kinase Signaling System/physiology ; Microscopy, Fluorescence ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Mitogen-Activated Protein Kinases/metabolism ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Nitriles/pharmacology ; PC12 Cells ; Peptide Fragments/pharmacology ; RNA Interference ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Adaptor Proteins, Signal Transducing ; Amyloid beta-Peptides ; Butadienes ; CDCA5 protein, human ; Cell Cycle Proteins ; Nitriles ; Peptide Fragments ; U 0126 ; amyloid beta-protein (1-42) ; Cyclin D1 (136601-57-5) ; Cyclin-Dependent Kinase 5 (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2012-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E12-02-0125
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2853: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 410: Show issues

Order via subito

Details ▾

Article ; Online: Respiratory syncytial virus infection down-regulates antioxidant enzyme expression by triggering deacetylation-proteasomal degradation of Nrf2.

Komaravelli, Narayana / Tian, Bing / Ivanciuc, Teodora / Mautemps, Nicholas / Brasier, Allan R / Garofalo, Roberto P / Casola, Antonella

Free radical biology & medicine

2015 Volume 88, Issue Pt B, Page(s) 391–403

Abstract: Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. RSV infection in cells, mice, and children leads to rapid ... ...

Abstract	Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. RSV infection in cells, mice, and children leads to rapid generation of reactive oxygen species, which are associated with oxidative stress and lung damage, due to a significant decrease in the expression of airway antioxidant enzymes (AOEs). Oxidative stress plays an important role in the pathogenesis of RSV-induced lung disease, as antioxidants ameliorate clinical disease and inflammation in vivo. The aim of this study is to investigate the unknown mechanism(s) of virus-induced inhibition of AOE expression. RSV infection is shown to induce a progressive reduction in nuclear and total cellular levels of the transcription factor NF-E2-related factor 2 (Nrf2), resulting in decreased binding to endogenous AOE gene promoters and decreased AOE expression. RSV induces Nrf2 deacetylation and degradation via the proteasome pathway in vitro and in vivo. Histone deacetylase and proteasome inhibitors block Nrf2 degradation and increase Nrf2 binding to AOE endogenous promoters, resulting in increased AOE expression. Known inducers of Nrf2 are able to increase Nrf2 activation and subsequent AOE expression during RSV infection in vitro and in vivo, with significant amelioration of oxidative stress. This is the first study to investigate the mechanism(s) of virus-induced inhibition of AOE expression. RSV-induced inhibition of Nrf2 activation, due to deacetylation and proteasomal degradation, could be targeted for therapeutic intervention aimed to increase airway antioxidant capacity during infection.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Blotting, Western ; Cell Line ; Chromatin Immunoprecipitation ; Down-Regulation ; Female ; Humans ; Immunoprecipitation ; Mice ; Mice, Inbred BALB C ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/physiology ; Proteasome Endopeptidase Complex/metabolism ; Respiratory Syncytial Virus Infections/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Antioxidants ; NF-E2-Related Factor 2 ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2015-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2015.05.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2109: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Antioxidant mimetics modulate oxidative stress and cellular signaling in airway epithelial cells infected with respiratory syncytial virus.

Hosakote, Yashoda M / Komaravelli, Narayana / Mautemps, Nicolas / Liu, Tianshuang / Garofalo, Roberto P / Casola, Antonella

American journal of physiology. Lung cellular and molecular physiology

2012 Volume 303, Issue 11, Page(s) L991–1000

Abstract: Respiratory syncytial virus (RSV) is one of the most common causes of bronchiolitis and pneumonia among infants and young children worldwide. In previous investigations, we have shown that RSV infection induces rapid generation of reactive oxygen species ...

Abstract	Respiratory syncytial virus (RSV) is one of the most common causes of bronchiolitis and pneumonia among infants and young children worldwide. In previous investigations, we have shown that RSV infection induces rapid generation of reactive oxygen species (ROS), which modulate viral-induced cellular signaling, and downregulation of antioxidant enzyme (AOE) expression, resulting in oxidative stress in vitro and in vivo, which plays a pathogenetic role in RSV-induced lung disease. In this study, we determined whether pharmacological intervention with synthetic catalytic scavengers could reduce RSV-induced proinflammatory gene expression and oxidative cell damage in an in vitro model of infection. Treatment of airway epithelial cells (AECs) with the salen-manganese complexes EUK-8 or EUK-189, which possess superoxide dismutase, catalase, and glutathione peroxidase activity, strongly reduced RSV-induced ROS formation by increasing cellular AOE enzymatic activity and levels of the lipid peroxidation products F(2)-8-isoprostane and malondialdehyde, which are markers of oxidative stress. Treatment of AECs with AOE mimetics also significantly inhibited RSV-induced cytokine and chemokine secretion and activation of the transcription factors nuclear factor-κB and interferon regulatory factor-3, which orchestrate proinflammatory gene expression. Both EUKs were able to reduce viral replication, when used at high doses. These results suggest that increasing antioxidant cellular capacities can significantly impact RSV-associated oxidative cell damage and cellular signaling and could represent a novel therapeutic approach in modulating virus-induced lung disease.
MeSH term(s)	Antioxidants/pharmacology ; Catalase/metabolism ; Cell Line ; Cytokines/metabolism ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Ethylenediamines/pharmacology ; F2-Isoprostanes/metabolism ; Gene Expression Regulation/drug effects ; Glutathione Peroxidase/metabolism ; Glutathione Transferase/metabolism ; Host-Pathogen Interactions/drug effects ; Humans ; Lipid Peroxidation ; Malondialdehyde/metabolism ; Molecular Mimicry ; NF-E2 Transcription Factor, p45 Subunit/metabolism ; Organometallic Compounds/pharmacology ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/pathology ; Respiratory Syncytial Virus Infections/metabolism ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Viruses/physiology ; Salicylates/pharmacology ; Signal Transduction ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1 ; Virus Replication/drug effects
Chemical Substances	Antioxidants ; Cytokines ; EUK-189 ; Ethylenediamines ; F2-Isoprostanes ; NF-E2 Transcription Factor, p45 Subunit ; NFE2 protein, human ; Organometallic Compounds ; Reactive Oxygen Species ; SOD1 protein, human ; Salicylates ; Malondialdehyde (4Y8F71G49Q) ; N,N'-bis(salicylideneamino)ethane-manganese(II) (53177-12-1) ; Catalase (EC 1.11.1.6) ; Glutathione Peroxidase (EC 1.11.1.9) ; SOD3 protein, human (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Glutathione Transferase (EC 2.5.1.18)
Language	English
Publishing date	2012-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00192.2012
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.A 2749: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito