GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules
Aims: γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecule...
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| Veröffentlicht in: | Cellular physiology and biochemistry 2014-01, Vol.33 (4), p.1117-1129 |
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| creator | Yang, Ying Lian, Yi-Tian Huang, Shi-Yuan Yang, Yong Cheng, Long-Xian Liu, Kun |
| description | Aims: γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs). Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions. |
| doi_str_mv | 10.1159/000358681 |
| format | Article |
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The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs). Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000358681</identifier><identifier>PMID: 24733016</identifier><language>eng</language><publisher>Basel, Switzerland: Cell Physiol Biochem Press GmbH & Co KG</publisher><subject>Atherosclerosis ; ATP Binding Cassette Transporter 1 - genetics ; ATP Binding Cassette Transporter 1 - metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; CD36 Antigens - genetics ; CD36 Antigens - metabolism ; Cholesterol ; Cholesterol - metabolism ; Down-Regulation - drug effects ; Foam Cells - cytology ; Foam Cells - drug effects ; Fructose - analogs & derivatives ; Fructose - pharmacology ; GABA ; GABA receptor agonist ; gamma-Aminobutyric Acid - pharmacology ; Humans ; Lipoproteins, LDL - pharmacology ; Macrophage ; Macrophages - cytology ; Neuroprotective Agents - pharmacology ; Original Paper ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphorylation - drug effects ; Scavenger Receptors, Class A - genetics ; Scavenger Receptors, Class A - metabolism ; Scavenger Receptors, Class E - genetics ; Scavenger Receptors, Class E - metabolism ; Signal Transduction ; Topiramate ; Tumor Necrosis Factor-alpha - metabolism ; Up-Regulation - drug effects</subject><ispartof>Cellular physiology and biochemistry, 2014-01, Vol.33 (4), p.1117-1129</ispartof><rights>2014 S. Karger AG, Basel</rights><rights>2014 S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-a43fd63e726c525d617d8a363da279077151c2303455e765af6204fcf2b9f1d13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2100,27634,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24733016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Lian, Yi-Tian</creatorcontrib><creatorcontrib>Huang, Shi-Yuan</creatorcontrib><creatorcontrib>Yang, Yong</creatorcontrib><creatorcontrib>Cheng, Long-Xian</creatorcontrib><creatorcontrib>Liu, Kun</creatorcontrib><title>GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Aims: γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs). Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.</description><subject>Atherosclerosis</subject><subject>ATP Binding Cassette Transporter 1 - genetics</subject><subject>ATP Binding Cassette Transporter 1 - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 1</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>CD36 Antigens - genetics</subject><subject>CD36 Antigens - metabolism</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Foam Cells - cytology</subject><subject>Foam Cells - drug effects</subject><subject>Fructose - analogs & derivatives</subject><subject>Fructose - pharmacology</subject><subject>GABA</subject><subject>GABA receptor agonist</subject><subject>gamma-Aminobutyric Acid - pharmacology</subject><subject>Humans</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Macrophage</subject><subject>Macrophages - cytology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Original Paper</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Scavenger Receptors, Class A - genetics</subject><subject>Scavenger Receptors, Class A - metabolism</subject><subject>Scavenger Receptors, Class E - genetics</subject><subject>Scavenger Receptors, Class E - metabolism</subject><subject>Signal Transduction</subject><subject>Topiramate</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Up-Regulation - drug effects</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNptkUtv1DAUhSMEog9YsEfIEhtYBPyI7WQ5DbQdqSNYlLV148eMSxJP7QSpf4FfXUNKVqxsX3_nXN17iuINwZ8I4c1njDHjtajJs-KUVJSUjZT183zHhJd1U8uT4iylO5yfsqEvixNaScYwEafF76vNxQbBaNBtOPoIA0wWbceD7_yEpoNFlyHmmg8jCg5dzwOMaAc6huMB9rb8YqP_ZU2mYECt7fuEuge0C2bus2jco_YQepsmG0Nf7uwEXeh9GspNSkH73MtkuLd6ztCr4oWDPtnXT-d58ePy6217Xd58u9q2m5tSV4xPJVTMGcGspEJzyo0g0tTABDNAZYOlJJxoyjCrOLdScHCC4sppR7vGEUPYebFdfE2AO3WMfoD4oAJ49bcQ4l5BnLzurcIdd9pmuW5kBYSDEUYzZ2kFdVWROnt9WLyOMdzPeVA1-KTzHmC0YU6KcFozJqRoMvpxQfPyUorWra0JVn9iVGuMmX33ZDt3gzUr-S-3DLxdgJ8Q9zauwKp__9_v9vvFQqijcewRD9-sRQ</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Yang, Ying</creator><creator>Lian, Yi-Tian</creator><creator>Huang, Shi-Yuan</creator><creator>Yang, Yong</creator><creator>Cheng, Long-Xian</creator><creator>Liu, Kun</creator><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</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><scope>DOA</scope></search><sort><creationdate>20140101</creationdate><title>GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules</title><author>Yang, Ying ; Lian, Yi-Tian ; Huang, Shi-Yuan ; Yang, Yong ; Cheng, Long-Xian ; Liu, Kun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-a43fd63e726c525d617d8a363da279077151c2303455e765af6204fcf2b9f1d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Atherosclerosis</topic><topic>ATP Binding Cassette Transporter 1 - genetics</topic><topic>ATP Binding Cassette Transporter 1 - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 1</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>CD36 Antigens - genetics</topic><topic>CD36 Antigens - metabolism</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Foam Cells - cytology</topic><topic>Foam Cells - drug effects</topic><topic>Fructose - analogs & derivatives</topic><topic>Fructose - pharmacology</topic><topic>GABA</topic><topic>GABA receptor agonist</topic><topic>gamma-Aminobutyric Acid - pharmacology</topic><topic>Humans</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Macrophage</topic><topic>Macrophages - cytology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Original Paper</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Scavenger Receptors, Class A - genetics</topic><topic>Scavenger Receptors, Class A - metabolism</topic><topic>Scavenger Receptors, Class E - genetics</topic><topic>Scavenger Receptors, Class E - metabolism</topic><topic>Signal Transduction</topic><topic>Topiramate</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Lian, Yi-Tian</creatorcontrib><creatorcontrib>Huang, Shi-Yuan</creatorcontrib><creatorcontrib>Yang, Yong</creatorcontrib><creatorcontrib>Cheng, Long-Xian</creatorcontrib><creatorcontrib>Liu, Kun</creatorcontrib><collection>Karger Open Access</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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Ying</au><au>Lian, Yi-Tian</au><au>Huang, Shi-Yuan</au><au>Yang, Yong</au><au>Cheng, Long-Xian</au><au>Liu, Kun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>33</volume><issue>4</issue><spage>1117</spage><epage>1129</epage><pages>1117-1129</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Aims: γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs). Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.</abstract><cop>Basel, Switzerland</cop><pub>Cell Physiol Biochem Press GmbH & Co KG</pub><pmid>24733016</pmid><doi>10.1159/000358681</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Atherosclerosis ATP Binding Cassette Transporter 1 - genetics ATP Binding Cassette Transporter 1 - metabolism ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism CD36 Antigens - genetics CD36 Antigens - metabolism Cholesterol Cholesterol - metabolism Down-Regulation - drug effects Foam Cells - cytology Foam Cells - drug effects Fructose - analogs & derivatives Fructose - pharmacology GABA GABA receptor agonist gamma-Aminobutyric Acid - pharmacology Humans Lipoproteins, LDL - pharmacology Macrophage Macrophages - cytology Neuroprotective Agents - pharmacology Original Paper p38 Mitogen-Activated Protein Kinases - metabolism Phosphorylation - drug effects Scavenger Receptors, Class A - genetics Scavenger Receptors, Class A - metabolism Scavenger Receptors, Class E - genetics Scavenger Receptors, Class E - metabolism Signal Transduction Topiramate Tumor Necrosis Factor-alpha - metabolism Up-Regulation - drug effects |
| title | GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules |
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