Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages

Publication type:
Journal article
Metadata:
Autoren
  • V Badireenath Konkimalla
  • Martina Blunder
  • Rudolf Bauer
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000276540800005&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.bcp.2010.01.020
eISSN
1873-2968
Externe Identifier
  • Clarivate Analytics Document Solution ID: 581RA
  • PubMed Identifier: 20105431
ISSN
0006-2952
Ausgabe der Veröffentlichung
11
Zeitschrift
BIOCHEMICAL PHARMACOLOGY
Schlüsselwörter
  • Cytotoxicity
  • Glucocorticoid receptor signaling pathway
  • Griess assay
  • Interleukin-10 signaling pathway
  • Microarrays
  • Nitric oxide
Paginierung
1573 - 1580
Datum der Veröffentlichung
2010
Status
Published
Titel
Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages
Sub types
  • Article
Ausgabe der Zeitschrift
79

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • V Badireenath Konkimalla
  • Martina Blunder
  • Rudolf Bauer
  • Thomas Efferth
DOI
10.1016/j.bcp.2010.01.020
ISSN
0006-2952
Ausgabe der Veröffentlichung
11
Zeitschrift
Biochemical Pharmacology
Sprache
en
Paginierung
1573 - 1580
Datum der Veröffentlichung
2010
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.bcp.2010.01.020
Datum der Datenerfassung
2020
Titel
Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages
Ausgabe der Zeitschrift
79

Data source: Crossref

Abstract
Nitric oxide (NO) plays a role in various physiological and pathophysiological conditions such as immunoregulatory and inflammatory processes. Hence, NO and its generating enzyme, inducible nitric oxide synthase (iNOS) may not only be of diagnostic and prognostic value, but may also serve as targets for novel therapeutic options. In the present investigation, we have screened a phytochemical library by correlating the IC(50) values for 531 natural products of 60 cell lines with the microarray-based mRNA expression of 95 genes known to be involved in NO metabolism and signaling with the aim to identify candidate compounds as inhibitors for NO metabolism and signaling. We identified bis(helenalinyl)glutarate (BHG) as putative candidate compound. Indeed, BHG inhibited NO production (IC(50) value: 0.90+/-0.04microM) and down-regulated iNOS protein expression (IC(50) value: 1.12+/-0.16microM) of RAW264.7 mouse macrophages in the presence of lipopolysaccharide and interferon-gamma. Performing XTT cytotoxicity assays, we found that BHG inhibited cell growth in a dose-dependent manner with an IC(50) value of 5.6microM. To gain insight into molecular pathways involved in NO inhibition and cytotoxicity, we performed microarray experiments which were exemplarily validated by real-time RT-PCR. A total of 227 genes (67 up- and 160 down-regulated) were obtained, which exhibited significant differences in mRNA regulation between BHG-treated and untreated RAW264.7 macrophages. Sixteen of 227 genes are known to be involved in NO-signaling. Pathway analyses revealed that further five and four down-regulated genes belong to the glucocorticoid receptor and interleukin-1 and interleukin-10 pathways, respectively. An interference of these two pathways and NO is known for inflammation and auto-immune diseases. The therapeutic potential of this compound has to be explored in the future.
Addresses
  • German Cancer Research Centre, Heidelberg, Germany.
Autoren
  • V Badireenath Konkimalla
  • Martina Blunder
  • Rudolf Bauer
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1016/j.bcp.2010.01.020
eISSN
1873-2968
Externe Identifier
  • PubMed Identifier: 20105431
Open access
false
ISSN
0006-2952
Ausgabe der Veröffentlichung
11
Zeitschrift
Biochemical pharmacology
Schlüsselwörter
  • Cell Line
  • Macrophages
  • Animals
  • Mice
  • Nitric Oxide
  • Sesquiterpenes
  • Lactones
  • Receptors, Glucocorticoid
  • Interleukin-1
  • Interleukin-10
  • Drug Evaluation, Preclinical
  • Gene Expression Profiling
  • Cell Proliferation
  • Gene Expression Regulation
  • Nitric Oxide Synthase Type II
  • Metabolic Networks and Pathways
Sprache
eng
Medium
Print-Electronic
Online publication date
2010
Paginierung
1573 - 1580
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2010
Titel
Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
79

Data source: Europe PubMed Central

Abstract
Nitric oxide (NO) plays a role in various physiological and pathophysiological conditions such as immunoregulatory and inflammatory processes. Hence, NO and its generating enzyme, inducible nitric oxide synthase (iNOS) may not only be of diagnostic and prognostic value, but may also serve as targets for novel therapeutic options. In the present investigation, we have screened a phytochemical library by correlating the IC(50) values for 531 natural products of 60 cell lines with the microarray-based mRNA expression of 95 genes known to be involved in NO metabolism and signaling with the aim to identify candidate compounds as inhibitors for NO metabolism and signaling. We identified bis(helenalinyl)glutarate (BHG) as putative candidate compound. Indeed, BHG inhibited NO production (IC(50) value: 0.90+/-0.04microM) and down-regulated iNOS protein expression (IC(50) value: 1.12+/-0.16microM) of RAW264.7 mouse macrophages in the presence of lipopolysaccharide and interferon-gamma. Performing XTT cytotoxicity assays, we found that BHG inhibited cell growth in a dose-dependent manner with an IC(50) value of 5.6microM. To gain insight into molecular pathways involved in NO inhibition and cytotoxicity, we performed microarray experiments which were exemplarily validated by real-time RT-PCR. A total of 227 genes (67 up- and 160 down-regulated) were obtained, which exhibited significant differences in mRNA regulation between BHG-treated and untreated RAW264.7 macrophages. Sixteen of 227 genes are known to be involved in NO-signaling. Pathway analyses revealed that further five and four down-regulated genes belong to the glucocorticoid receptor and interleukin-1 and interleukin-10 pathways, respectively. An interference of these two pathways and NO is known for inflammation and auto-immune diseases. The therapeutic potential of this compound has to be explored in the future.
Date of acceptance
2010
Autoren
  • V Badireenath Konkimalla
  • Martina Blunder
  • Rudolf Bauer
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/20105431
DOI
10.1016/j.bcp.2010.01.020
eISSN
1873-2968
Ausgabe der Veröffentlichung
11
Zeitschrift
Biochem Pharmacol
Schlüsselwörter
  • Animals
  • Cell Line
  • Cell Proliferation
  • Drug Evaluation, Preclinical
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Interleukin-1
  • Interleukin-10
  • Lactones
  • Macrophages
  • Metabolic Networks and Pathways
  • Mice
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Receptors, Glucocorticoid
  • Sesquiterpenes
Sprache
eng
Country
England
Paginierung
1573 - 1580
PII
S0006-2952(10)00058-4
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
79

Data source: PubMed

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