Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs
We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of isolated pulmonary arteries. In the present investigations, we identifie...
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| Veröffentlicht in: | American journal of respiratory cell and molecular biology 1998-07, Vol.19 (1), p.121-128 |
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| creator | Zhu, Daling Effros, Richard M Harder, David R Roman, Richard J Jacobs, Elizabeth R |
| description | We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of isolated pulmonary arteries. In the present investigations, we identified sources of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large vessels, and lysates of alveolar macrophages all express proteins of approximately 50 kD which cross-reacted with a primary antibody raised against rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries, airways, and isolated vascular smooth muscle cells from small pulmonary arteries produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was readily detectable by reverse transcription-polymerase chain reaction using isoform-specific probes and 5 microg total RNA extracted from microdissected small pulmonary arteries. These data demonstrate that small pulmonary arteries express cP450 4A proteins and vascular smooth muscle cells derived from these arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely distributed in rabbit tissue, raising the possibility that 20-HETE generated from nonvascular tissue could serve as a paracrine factor in the pulmonary circulation. |
| doi_str_mv | 10.1165/ajrcmb.19.1.3145 |
| format | Article |
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In the present investigations, we identified sources of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large vessels, and lysates of alveolar macrophages all express proteins of approximately 50 kD which cross-reacted with a primary antibody raised against rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries, airways, and isolated vascular smooth muscle cells from small pulmonary arteries produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was readily detectable by reverse transcription-polymerase chain reaction using isoform-specific probes and 5 microg total RNA extracted from microdissected small pulmonary arteries. These data demonstrate that small pulmonary arteries express cP450 4A proteins and vascular smooth muscle cells derived from these arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely distributed in rabbit tissue, raising the possibility that 20-HETE generated from nonvascular tissue could serve as a paracrine factor in the pulmonary circulation.</description><identifier>ISSN: 1044-1549</identifier><identifier>EISSN: 1535-4989</identifier><identifier>DOI: 10.1165/ajrcmb.19.1.3145</identifier><identifier>PMID: 9651188</identifier><identifier>CODEN: AJRBEL</identifier><language>eng</language><publisher>United States: Am Thoracic Soc</publisher><subject>Animals ; Arachidonic Acid - metabolism ; Cytochrome P-450 CYP4A ; Cytochrome P-450 Enzyme System - metabolism ; Hydroxyeicosatetraenoic Acids - biosynthesis ; Lung - blood supply ; Lung - metabolism ; Macrophages, Alveolar - metabolism ; Male ; Microsomes - metabolism ; Mixed Function Oxygenases - metabolism ; Muscle, Smooth, Vascular - metabolism ; Polymerase Chain Reaction ; Pulmonary Artery - metabolism ; Rabbits</subject><ispartof>American journal of respiratory cell and molecular biology, 1998-07, Vol.19 (1), p.121-128</ispartof><rights>Copyright American Lung Association Jul 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-a48a96f5fc5cc51df499d15b18b6f0e5167bb6d296ed8455b1de55cfa4fd3dc13</citedby><cites>FETCH-LOGICAL-c354t-a48a96f5fc5cc51df499d15b18b6f0e5167bb6d296ed8455b1de55cfa4fd3dc13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9651188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Daling</creatorcontrib><creatorcontrib>Effros, Richard M</creatorcontrib><creatorcontrib>Harder, David R</creatorcontrib><creatorcontrib>Roman, Richard J</creatorcontrib><creatorcontrib>Jacobs, Elizabeth R</creatorcontrib><title>Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of isolated pulmonary arteries. In the present investigations, we identified sources of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large vessels, and lysates of alveolar macrophages all express proteins of approximately 50 kD which cross-reacted with a primary antibody raised against rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries, airways, and isolated vascular smooth muscle cells from small pulmonary arteries produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was readily detectable by reverse transcription-polymerase chain reaction using isoform-specific probes and 5 microg total RNA extracted from microdissected small pulmonary arteries. These data demonstrate that small pulmonary arteries express cP450 4A proteins and vascular smooth muscle cells derived from these arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely distributed in rabbit tissue, raising the possibility that 20-HETE generated from nonvascular tissue could serve as a paracrine factor in the pulmonary circulation.</description><subject>Animals</subject><subject>Arachidonic Acid - metabolism</subject><subject>Cytochrome P-450 CYP4A</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Hydroxyeicosatetraenoic Acids - biosynthesis</subject><subject>Lung - blood supply</subject><subject>Lung - metabolism</subject><subject>Macrophages, Alveolar - metabolism</subject><subject>Male</subject><subject>Microsomes - metabolism</subject><subject>Mixed Function Oxygenases - metabolism</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Pulmonary Artery - metabolism</subject><subject>Rabbits</subject><issn>1044-1549</issn><issn>1535-4989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</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>eNpdkEtLAzEUhYMo9bl3IwQX4mZq7kySTpal1BcFxdZ1yOTRTplHTWaQ_ntTW1y4uhfOdw73HoSugQwBOHtQa6_rYghiCMMMKDtCZ8AyllCRi-O4E0oTYFScovMQ1oRAmgMM0EBwBpDnZ-h1UYbQWzxve69twK3Dk23X6pVva4vfKSOYjrFqDE5J8jxdTPF823QrG8qAywZ_qKIoOzzrm2W4RCdOVcFeHeYF-nycLibPyezt6WUyniU6Y7RLFM2V4I45zbRmYBwVwgArIC-4I5YBHxUFN6ng1uSURcFYxrRT1JnMaMgu0N0-d-Pbr96GTtZl0LaqVGPbPsiRECORpjSCt__AdfyyibfJlIw4jSCPENlD2rcheOvkxpe18lsJRO46lvuOJQgJctdxtNwccvuitubPcCg16vd7fVUuV9-ltzLUqqoiDYew3yxIIfsB1wWEmA</recordid><startdate>19980701</startdate><enddate>19980701</enddate><creator>Zhu, Daling</creator><creator>Effros, Richard M</creator><creator>Harder, David R</creator><creator>Roman, Richard J</creator><creator>Jacobs, Elizabeth R</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></search><sort><creationdate>19980701</creationdate><title>Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs</title><author>Zhu, Daling ; Effros, Richard M ; Harder, David R ; Roman, Richard J ; Jacobs, Elizabeth R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-a48a96f5fc5cc51df499d15b18b6f0e5167bb6d296ed8455b1de55cfa4fd3dc13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Arachidonic Acid - metabolism</topic><topic>Cytochrome P-450 CYP4A</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Hydroxyeicosatetraenoic Acids - biosynthesis</topic><topic>Lung - blood supply</topic><topic>Lung - metabolism</topic><topic>Macrophages, Alveolar - metabolism</topic><topic>Male</topic><topic>Microsomes - metabolism</topic><topic>Mixed Function Oxygenases - metabolism</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Pulmonary Artery - metabolism</topic><topic>Rabbits</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Daling</creatorcontrib><creatorcontrib>Effros, Richard M</creatorcontrib><creatorcontrib>Harder, David R</creatorcontrib><creatorcontrib>Roman, Richard J</creatorcontrib><creatorcontrib>Jacobs, Elizabeth R</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</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><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Daling</au><au>Effros, Richard M</au><au>Harder, David R</au><au>Roman, Richard J</au><au>Jacobs, Elizabeth R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>1998-07-01</date><risdate>1998</risdate><volume>19</volume><issue>1</issue><spage>121</spage><epage>128</epage><pages>121-128</pages><issn>1044-1549</issn><eissn>1535-4989</eissn><coden>AJRBEL</coden><abstract>We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of isolated pulmonary arteries. In the present investigations, we identified sources of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large vessels, and lysates of alveolar macrophages all express proteins of approximately 50 kD which cross-reacted with a primary antibody raised against rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries, airways, and isolated vascular smooth muscle cells from small pulmonary arteries produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was readily detectable by reverse transcription-polymerase chain reaction using isoform-specific probes and 5 microg total RNA extracted from microdissected small pulmonary arteries. These data demonstrate that small pulmonary arteries express cP450 4A proteins and vascular smooth muscle cells derived from these arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely distributed in rabbit tissue, raising the possibility that 20-HETE generated from nonvascular tissue could serve as a paracrine factor in the pulmonary circulation.</abstract><cop>United States</cop><pub>Am Thoracic Soc</pub><pmid>9651188</pmid><doi>10.1165/ajrcmb.19.1.3145</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 1044-1549 |
| ispartof | American journal of respiratory cell and molecular biology, 1998-07, Vol.19 (1), p.121-128 |
| issn | 1044-1549 1535-4989 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Animals Arachidonic Acid - metabolism Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System - metabolism Hydroxyeicosatetraenoic Acids - biosynthesis Lung - blood supply Lung - metabolism Macrophages, Alveolar - metabolism Male Microsomes - metabolism Mixed Function Oxygenases - metabolism Muscle, Smooth, Vascular - metabolism Polymerase Chain Reaction Pulmonary Artery - metabolism Rabbits |
| title | Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs |
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