Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells
S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl le...
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| Veröffentlicht in: | American journal of respiratory cell and molecular biology 2006-04, Vol.34 (4), p.387-393 |
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| container_title | American journal of respiratory cell and molecular biology |
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| creator | Zaman, Khalequz Hanigan, Marie H Smith, Alison Vaughan, John Macdonald, Timothy Jones, David R Hunt, John F Gaston, Benjamin |
| description | S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting. |
| doi_str_mv | 10.1165/rcmb.2005-0336RC |
| format | Article |
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Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels<or=1 microM, likely recapitulating those in the asthmatic airway, increase 5-LO expression, an effect that may increase inflammation and bronchoconstriction. However, GSNO at concentrations>5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting.</description><identifier>ISSN: 1044-1549</identifier><identifier>EISSN: 1535-4989</identifier><identifier>DOI: 10.1165/rcmb.2005-0336RC</identifier><identifier>PMID: 16415251</identifier><identifier>CODEN: AJRBEL</identifier><language>eng</language><publisher>United States: Am Thoracic Soc</publisher><subject>Arachidonate 5-Lipoxygenase - biosynthesis ; Bronchodilator Agents - pharmacology ; Cells, Cultured ; Enzyme Activation ; Epithelial Cells - drug effects ; Epithelial Cells - enzymology ; gamma-Glutamyltransferase - antagonists & inhibitors ; gamma-Glutamyltransferase - metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Nitric Oxide Donors - pharmacology ; Plicamycin - analogs & derivatives ; Plicamycin - pharmacology ; Proteasome Endopeptidase Complex - physiology ; Rapid Communication ; Respiratory Mucosa - drug effects ; Respiratory Mucosa - enzymology ; S-Nitrosoglutathione - metabolism ; S-Nitrosoglutathione - pharmacology ; Sp1 Transcription Factor - physiology ; Sp3 Transcription Factor - physiology</subject><ispartof>American journal of respiratory cell and molecular biology, 2006-04, Vol.34 (4), p.387-393</ispartof><rights>Copyright American Thoracic Society Apr 2006</rights><rights>Copyright © 2006, American Thoracic Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-bec43f1b0e5a5b33d04e1d219eb50ae7ad12f41a41056e03ba560ef741e305403</citedby><cites>FETCH-LOGICAL-c454t-bec43f1b0e5a5b33d04e1d219eb50ae7ad12f41a41056e03ba560ef741e305403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16415251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zaman, Khalequz</creatorcontrib><creatorcontrib>Hanigan, Marie H</creatorcontrib><creatorcontrib>Smith, Alison</creatorcontrib><creatorcontrib>Vaughan, John</creatorcontrib><creatorcontrib>Macdonald, Timothy</creatorcontrib><creatorcontrib>Jones, David R</creatorcontrib><creatorcontrib>Hunt, John F</creatorcontrib><creatorcontrib>Gaston, Benjamin</creatorcontrib><title>Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels<or=1 microM, likely recapitulating those in the asthmatic airway, increase 5-LO expression, an effect that may increase inflammation and bronchoconstriction. However, GSNO at concentrations>5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting.</description><subject>Arachidonate 5-Lipoxygenase - biosynthesis</subject><subject>Bronchodilator Agents - pharmacology</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - enzymology</subject><subject>gamma-Glutamyltransferase - antagonists & inhibitors</subject><subject>gamma-Glutamyltransferase - metabolism</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Plicamycin - analogs & derivatives</subject><subject>Plicamycin - pharmacology</subject><subject>Proteasome Endopeptidase Complex - physiology</subject><subject>Rapid Communication</subject><subject>Respiratory Mucosa - drug effects</subject><subject>Respiratory Mucosa - enzymology</subject><subject>S-Nitrosoglutathione - metabolism</subject><subject>S-Nitrosoglutathione - pharmacology</subject><subject>Sp1 Transcription Factor - physiology</subject><subject>Sp3 Transcription Factor - physiology</subject><issn>1044-1549</issn><issn>1535-4989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkUmP1DAQhS0EYoaBOycUcUBcMlR5SToXpFGrWaQGJJYjspyk0nHLiYOdMNP_Hre6xXZySf7qqd57jD1FuEYs1KvQDPU1B1A5CFF8Xt9jl6iEymW1qu6nGaTMUcnqgj2KcQ-AfIX4kF1gIVFxhZfs-2Zs_Y5Gv8TsS_7RzsFHv3PLbObe-pGyD761naWYqXxrJ393SLCJlG3upkAxJiazY3Zjw605ZJvJzj05a1y2JufiY_agMy7Sk_N7xb692Xxdv8u3n96-X99s80YqOec1NVJ0WAMpo2ohWpCELceKagWGStMi7yQaiaAKAlEbVQB1pUQSoCSIK_b6pDst9UBtQ-McjNNTsIMJB-2N1f_-jLbXO_9T80JKDjwJvDgLBP9joTjrwcYmWTAjpWh0UZaqSmkm8Pl_4N4vYUzmNIdSraoKMUFwgpqUZgzU_b4EQR-L08fi9LE4fSourTz728GfhXNTCXh5Anq7629tIB0H41zCUZv9UU9ILbVYleIXmV6krw</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>Zaman, Khalequz</creator><creator>Hanigan, Marie H</creator><creator>Smith, Alison</creator><creator>Vaughan, John</creator><creator>Macdonald, Timothy</creator><creator>Jones, David R</creator><creator>Hunt, John F</creator><creator>Gaston, Benjamin</creator><general>Am Thoracic Soc</general><general>American Thoracic Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060401</creationdate><title>Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells</title><author>Zaman, Khalequz ; Hanigan, Marie H ; Smith, Alison ; Vaughan, John ; Macdonald, Timothy ; Jones, David R ; Hunt, John F ; Gaston, Benjamin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-bec43f1b0e5a5b33d04e1d219eb50ae7ad12f41a41056e03ba560ef741e305403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Arachidonate 5-Lipoxygenase - biosynthesis</topic><topic>Bronchodilator Agents - pharmacology</topic><topic>Cells, Cultured</topic><topic>Enzyme Activation</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - enzymology</topic><topic>gamma-Glutamyltransferase - antagonists & inhibitors</topic><topic>gamma-Glutamyltransferase - metabolism</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Humans</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Plicamycin - analogs & derivatives</topic><topic>Plicamycin - pharmacology</topic><topic>Proteasome Endopeptidase Complex - physiology</topic><topic>Rapid Communication</topic><topic>Respiratory Mucosa - drug effects</topic><topic>Respiratory Mucosa - enzymology</topic><topic>S-Nitrosoglutathione - metabolism</topic><topic>S-Nitrosoglutathione - pharmacology</topic><topic>Sp1 Transcription Factor - physiology</topic><topic>Sp3 Transcription Factor - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zaman, Khalequz</creatorcontrib><creatorcontrib>Hanigan, Marie H</creatorcontrib><creatorcontrib>Smith, Alison</creatorcontrib><creatorcontrib>Vaughan, John</creatorcontrib><creatorcontrib>Macdonald, Timothy</creatorcontrib><creatorcontrib>Jones, David R</creatorcontrib><creatorcontrib>Hunt, John F</creatorcontrib><creatorcontrib>Gaston, Benjamin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zaman, Khalequz</au><au>Hanigan, Marie H</au><au>Smith, Alison</au><au>Vaughan, John</au><au>Macdonald, Timothy</au><au>Jones, David R</au><au>Hunt, John F</au><au>Gaston, Benjamin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>34</volume><issue>4</issue><spage>387</spage><epage>393</epage><pages>387-393</pages><issn>1044-1549</issn><eissn>1535-4989</eissn><coden>AJRBEL</coden><abstract>S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels<or=1 microM, likely recapitulating those in the asthmatic airway, increase 5-LO expression, an effect that may increase inflammation and bronchoconstriction. However, GSNO at concentrations>5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting.</abstract><cop>United States</cop><pub>Am Thoracic Soc</pub><pmid>16415251</pmid><doi>10.1165/rcmb.2005-0336RC</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload; Alma/SFX Local Collection |
| subjects | Arachidonate 5-Lipoxygenase - biosynthesis Bronchodilator Agents - pharmacology Cells, Cultured Enzyme Activation Epithelial Cells - drug effects Epithelial Cells - enzymology gamma-Glutamyltransferase - antagonists & inhibitors gamma-Glutamyltransferase - metabolism Gene Expression Regulation, Enzymologic Humans Nitric Oxide Donors - pharmacology Plicamycin - analogs & derivatives Plicamycin - pharmacology Proteasome Endopeptidase Complex - physiology Rapid Communication Respiratory Mucosa - drug effects Respiratory Mucosa - enzymology S-Nitrosoglutathione - metabolism S-Nitrosoglutathione - pharmacology Sp1 Transcription Factor - physiology Sp3 Transcription Factor - physiology |
| title | Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells |
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