5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase
5‐Lipoxygenase (5‐LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5‐LO catalyzing both the synthesis of (5S)‐5‐hydroperoxy 6,8,11,14‐eicosatetraenoic acid (5‐HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5‐HPETE. We have...
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| Veröffentlicht in: | European journal of biochemistry 1993-07, Vol.215 (1), p.105-111 |
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| container_title | European journal of biochemistry |
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| creator | ABRAMOVITZ, Mark WONG, Elizabeth COX, Martha E. RICHARDSON, Christopher D. LI, Chun VICKERS, Philip J. |
| description | 5‐Lipoxygenase (5‐LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5‐LO catalyzing both the synthesis of (5S)‐5‐hydroperoxy 6,8,11,14‐eicosatetraenoic acid (5‐HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5‐HPETE. We have previously expressed both human 5‐LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5‐LO, we compared cellular 5‐LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5‐LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5‐LO as a substrate, and increases the efficiency with which 5‐LO converts 5‐HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5‐LO is inhibited by 3‐[1‐p‐chlorophenyl)‐5‐isopropyl‐3‐tert‐butylthio‐1H‐indol‐2‐yl]‐2,2‐dimethyl‐propanoic acid (MK‐886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5‐LO by acting as an arachidonic acid transfer protein. |
| doi_str_mv | 10.1111/j.1432-1033.1993.tb18012.x |
| format | Article |
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We have previously expressed both human 5‐LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5‐LO, we compared cellular 5‐LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5‐LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5‐LO as a substrate, and increases the efficiency with which 5‐LO converts 5‐HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5‐LO is inhibited by 3‐[1‐p‐chlorophenyl)‐5‐isopropyl‐3‐tert‐butylthio‐1H‐indol‐2‐yl]‐2,2‐dimethyl‐propanoic acid (MK‐886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5‐LO by acting as an arachidonic acid transfer protein.</description><identifier>ISSN: 0014-2956</identifier><identifier>EISSN: 1432-1033</identifier><identifier>DOI: 10.1111/j.1432-1033.1993.tb18012.x</identifier><identifier>PMID: 8344271</identifier><identifier>CODEN: EJBCAI</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>5-Lipoxygenase-Activating Proteins ; Analytical, structural and metabolic biochemistry ; Animals ; Arachidonate 5-Lipoxygenase - metabolism ; Arachidonic Acid - metabolism ; Biological and medical sciences ; Carrier Proteins - pharmacology ; Cell Line ; Enzyme Activation - drug effects ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. Psychology ; Humans ; Leukotrienes - biosynthesis ; Membrane Proteins - pharmacology ; Models, Biological ; Moths ; Neutrophils - metabolism ; Oxidoreductases ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacology</subject><ispartof>European journal of biochemistry, 1993-07, Vol.215 (1), p.105-111</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5175-da0b0b3fc5697f3a5abb58df3a050b0a17c4da8d37bc3b6c5ec0e7a292c73cd43</citedby><cites>FETCH-LOGICAL-c5175-da0b0b3fc5697f3a5abb58df3a050b0a17c4da8d37bc3b6c5ec0e7a292c73cd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4863681$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8344271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABRAMOVITZ, Mark</creatorcontrib><creatorcontrib>WONG, Elizabeth</creatorcontrib><creatorcontrib>COX, Martha E.</creatorcontrib><creatorcontrib>RICHARDSON, Christopher D.</creatorcontrib><creatorcontrib>LI, Chun</creatorcontrib><creatorcontrib>VICKERS, Philip J.</creatorcontrib><title>5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase</title><title>European journal of biochemistry</title><addtitle>Eur J Biochem</addtitle><description>5‐Lipoxygenase (5‐LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5‐LO catalyzing both the synthesis of (5S)‐5‐hydroperoxy 6,8,11,14‐eicosatetraenoic acid (5‐HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5‐HPETE. We have previously expressed both human 5‐LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5‐LO, we compared cellular 5‐LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5‐LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5‐LO as a substrate, and increases the efficiency with which 5‐LO converts 5‐HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5‐LO is inhibited by 3‐[1‐p‐chlorophenyl)‐5‐isopropyl‐3‐tert‐butylthio‐1H‐indol‐2‐yl]‐2,2‐dimethyl‐propanoic acid (MK‐886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5‐LO by acting as an arachidonic acid transfer protein.</description><subject>5-Lipoxygenase-Activating Proteins</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Arachidonate 5-Lipoxygenase - metabolism</subject><subject>Arachidonic Acid - metabolism</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - pharmacology</subject><subject>Cell Line</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Leukotrienes - biosynthesis</subject><subject>Membrane Proteins - pharmacology</subject><subject>Models, Biological</subject><subject>Moths</subject><subject>Neutrophils - metabolism</subject><subject>Oxidoreductases</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombinant Proteins - pharmacology</subject><issn>0014-2956</issn><issn>1432-1033</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE9P2zAYh61pqHTdPsIkC03cEuw4jhMuCFC7TarEge1svXYc6ipNSuxAy4mPwGfcJ5mjRhVXfLGt3_P-0YPQGSUxDediHdOUJREljMW0KFjsFc0JTeLdJzQ9Rp_RlBCaRknBs1P0xbk1ISQrMjFBk5ylaSLoFK34v9e3pd22u_2DacCZ8AXt7RN42zzgbdd6YxvsvN30NXjjsF8Z3Htb25eAtA1uKwwd6JUt28ZqDNqWWO3x0Ld-1_crOqmgdubbeM_Q38X8z-2vaHn38_ft9TLSnAoelUAUUazSPCtExYCDUjwvw4vwkAAVOi0hL5lQmqlMc6OJEZAUiRZMlymbofND37D6Y2-clxvrtKlraEzbOyl4Lgpe8ABeHkDdtc51ppLbzm6g20tK5KBZruXgUg4u5aBZjprlLhR_H6f0amPKY-noNeQ_xhychrrqoNHWHbE0z1iWD9jVAXu2tdl_YAG5mN_cU8LZf9fgn8M</recordid><startdate>199307</startdate><enddate>199307</enddate><creator>ABRAMOVITZ, Mark</creator><creator>WONG, Elizabeth</creator><creator>COX, Martha E.</creator><creator>RICHARDSON, Christopher D.</creator><creator>LI, Chun</creator><creator>VICKERS, Philip J.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>199307</creationdate><title>5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase</title><author>ABRAMOVITZ, Mark ; WONG, Elizabeth ; COX, Martha E. ; RICHARDSON, Christopher D. ; LI, Chun ; VICKERS, Philip J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5175-da0b0b3fc5697f3a5abb58df3a050b0a17c4da8d37bc3b6c5ec0e7a292c73cd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>5-Lipoxygenase-Activating Proteins</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Arachidonate 5-Lipoxygenase - metabolism</topic><topic>Arachidonic Acid - metabolism</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - pharmacology</topic><topic>Cell Line</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Leukotrienes - biosynthesis</topic><topic>Membrane Proteins - pharmacology</topic><topic>Models, Biological</topic><topic>Moths</topic><topic>Neutrophils - metabolism</topic><topic>Oxidoreductases</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ABRAMOVITZ, Mark</creatorcontrib><creatorcontrib>WONG, Elizabeth</creatorcontrib><creatorcontrib>COX, Martha E.</creatorcontrib><creatorcontrib>RICHARDSON, Christopher D.</creatorcontrib><creatorcontrib>LI, Chun</creatorcontrib><creatorcontrib>VICKERS, Philip J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABRAMOVITZ, Mark</au><au>WONG, Elizabeth</au><au>COX, Martha E.</au><au>RICHARDSON, Christopher D.</au><au>LI, Chun</au><au>VICKERS, Philip J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase</atitle><jtitle>European journal of biochemistry</jtitle><addtitle>Eur J Biochem</addtitle><date>1993-07</date><risdate>1993</risdate><volume>215</volume><issue>1</issue><spage>105</spage><epage>111</epage><pages>105-111</pages><issn>0014-2956</issn><eissn>1432-1033</eissn><coden>EJBCAI</coden><abstract>5‐Lipoxygenase (5‐LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5‐LO catalyzing both the synthesis of (5S)‐5‐hydroperoxy 6,8,11,14‐eicosatetraenoic acid (5‐HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5‐HPETE. We have previously expressed both human 5‐LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5‐LO, we compared cellular 5‐LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5‐LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5‐LO as a substrate, and increases the efficiency with which 5‐LO converts 5‐HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5‐LO is inhibited by 3‐[1‐p‐chlorophenyl)‐5‐isopropyl‐3‐tert‐butylthio‐1H‐indol‐2‐yl]‐2,2‐dimethyl‐propanoic acid (MK‐886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5‐LO by acting as an arachidonic acid transfer protein.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>8344271</pmid><doi>10.1111/j.1432-1033.1993.tb18012.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of biochemistry, 1993-07, Vol.215 (1), p.105-111 |
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| subjects | 5-Lipoxygenase-Activating Proteins Analytical, structural and metabolic biochemistry Animals Arachidonate 5-Lipoxygenase - metabolism Arachidonic Acid - metabolism Biological and medical sciences Carrier Proteins - pharmacology Cell Line Enzyme Activation - drug effects Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Humans Leukotrienes - biosynthesis Membrane Proteins - pharmacology Models, Biological Moths Neutrophils - metabolism Oxidoreductases Recombinant Proteins - metabolism Recombinant Proteins - pharmacology |
| title | 5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase |
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