Identification of Novel Human High-Density Lipoprotein Receptor Up-regulators Using a Cell-Based High-Throughput Screening Assay
Scavenger receptor class B type I (SR-BI) is the high-affinity high-density lipoprotein (HDL) receptor, and CLA-1 is the human homologue of the murine SR-BI. CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall...
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| Veröffentlicht in: | Journal of biomolecular screening 2007-03, Vol.12 (2), p.211-219 |
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| creator | Yang, Yuan Zhang, Zhongbing Jiang, Wei Gao, Lei Zhao, Guiyu Zheng, Zhihui Wang, Min Si, Shuyi Hong, Bin |
| description | Scavenger receptor class B type I (SR-BI) is the high-affinity high-density lipoprotein (HDL) receptor, and CLA-1 is the human homologue of the murine SR-BI. CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall HDL cholesterol (HDL-C) metabolism and its antiatherogenic activity in vivo. To search for active compounds that can increase CLA-1 transcription, a novel cell-based assay was developed for application in high-throughput screening (HTS). Human hepatoma HepG2 cells were transfected with a CLA-1-promoter-luciferase reporter gene construct, and the stable transfected cell line was selected and named CLAp-LUC HepG2. With rosiglitazone as a positive control, this stable cell line was used to establish a specific CLA-1 gene expression assay in a 96-well microplate format. The evaluating parameter Z' value of 0.64 showed that this cell-based HTS assay was robust and reliable. Screening of 6000 microbial secondary metabolite crude extracts identified 8 positive strains. Between 2 identified CLA-1 up-regulators produced by actinomycete strain 04-4776, 4776B may stimulate not only the expression of CLA-1 on the transcriptional and translational levels but also the activity of CLA-1 to uptake the HDL-C in HepG2 cells. The active compounds originated from this HTS assay may be developed to drug candidates or lead compounds for new antiatherosclerosis agents. |
| doi_str_mv | 10.1177/1087057106297568 |
| format | Article |
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CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall HDL cholesterol (HDL-C) metabolism and its antiatherogenic activity in vivo. To search for active compounds that can increase CLA-1 transcription, a novel cell-based assay was developed for application in high-throughput screening (HTS). Human hepatoma HepG2 cells were transfected with a CLA-1-promoter-luciferase reporter gene construct, and the stable transfected cell line was selected and named CLAp-LUC HepG2. With rosiglitazone as a positive control, this stable cell line was used to establish a specific CLA-1 gene expression assay in a 96-well microplate format. The evaluating parameter Z' value of 0.64 showed that this cell-based HTS assay was robust and reliable. Screening of 6000 microbial secondary metabolite crude extracts identified 8 positive strains. Between 2 identified CLA-1 up-regulators produced by actinomycete strain 04-4776, 4776B may stimulate not only the expression of CLA-1 on the transcriptional and translational levels but also the activity of CLA-1 to uptake the HDL-C in HepG2 cells. The active compounds originated from this HTS assay may be developed to drug candidates or lead compounds for new antiatherosclerosis agents.</description><identifier>ISSN: 1087-0571</identifier><identifier>ISSN: 2472-5552</identifier><identifier>EISSN: 1552-454X</identifier><identifier>DOI: 10.1177/1087057106297568</identifier><identifier>PMID: 17259591</identifier><language>eng</language><publisher>Thousand Oaks, CA: Sage Publications</publisher><subject>Actinomycetaceae - metabolism ; Actinomycetes ; Atherosclerosis ; Biological Assay - methods ; Blood lipoproteins ; Carbocyanines ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Fermentation ; Fluorescent Dyes ; Gene Expression Regulation - drug effects ; Genes, Reporter ; Humans ; Hydroxyl Radical - chemistry ; Isoflavones - isolation & purification ; Isoflavones - pharmacology ; Lipoproteins ; Lipoproteins, HDL - genetics ; Lipoproteins, HDL - metabolism ; Liver Neoplasms - pathology ; Luciferases - metabolism ; Metabolites ; PPAR gamma - agonists ; Proteolipids ; Receptors, Lipoprotein - genetics ; Receptors, Lipoprotein - metabolism ; Recombinant Fusion Proteins - metabolism ; Scavenger Receptors, Class B - genetics ; Scavenger Receptors, Class B - metabolism ; Thiazolidinediones - pharmacology ; Transcription, Genetic - drug effects ; Up-Regulation</subject><ispartof>Journal of biomolecular screening, 2007-03, Vol.12 (2), p.211-219</ispartof><rights>COPYRIGHT 2007 Sage Publications, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-5f5a1f211c5a0ac25d2f718355dce563ca7f815c9e42dbf67513faac41b86fa53</citedby><cites>FETCH-LOGICAL-c513t-5f5a1f211c5a0ac25d2f718355dce563ca7f815c9e42dbf67513faac41b86fa53</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/17259591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Yuan</creatorcontrib><creatorcontrib>Zhang, Zhongbing</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><creatorcontrib>Zhao, Guiyu</creatorcontrib><creatorcontrib>Zheng, Zhihui</creatorcontrib><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Si, Shuyi</creatorcontrib><creatorcontrib>Hong, Bin</creatorcontrib><title>Identification of Novel Human High-Density Lipoprotein Receptor Up-regulators Using a Cell-Based High-Throughput Screening Assay</title><title>Journal of biomolecular screening</title><addtitle>J Biomol Screen</addtitle><description>Scavenger receptor class B type I (SR-BI) is the high-affinity high-density lipoprotein (HDL) receptor, and CLA-1 is the human homologue of the murine SR-BI. CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall HDL cholesterol (HDL-C) metabolism and its antiatherogenic activity in vivo. To search for active compounds that can increase CLA-1 transcription, a novel cell-based assay was developed for application in high-throughput screening (HTS). Human hepatoma HepG2 cells were transfected with a CLA-1-promoter-luciferase reporter gene construct, and the stable transfected cell line was selected and named CLAp-LUC HepG2. With rosiglitazone as a positive control, this stable cell line was used to establish a specific CLA-1 gene expression assay in a 96-well microplate format. The evaluating parameter Z' value of 0.64 showed that this cell-based HTS assay was robust and reliable. Screening of 6000 microbial secondary metabolite crude extracts identified 8 positive strains. Between 2 identified CLA-1 up-regulators produced by actinomycete strain 04-4776, 4776B may stimulate not only the expression of CLA-1 on the transcriptional and translational levels but also the activity of CLA-1 to uptake the HDL-C in HepG2 cells. The active compounds originated from this HTS assay may be developed to drug candidates or lead compounds for new antiatherosclerosis agents.</description><subject>Actinomycetaceae - metabolism</subject><subject>Actinomycetes</subject><subject>Atherosclerosis</subject><subject>Biological Assay - methods</subject><subject>Blood lipoproteins</subject><subject>Carbocyanines</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical</subject><subject>Fermentation</subject><subject>Fluorescent Dyes</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Hydroxyl Radical - chemistry</subject><subject>Isoflavones - isolation & purification</subject><subject>Isoflavones - pharmacology</subject><subject>Lipoproteins</subject><subject>Lipoproteins, HDL - genetics</subject><subject>Lipoproteins, HDL - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Luciferases - metabolism</subject><subject>Metabolites</subject><subject>PPAR gamma - agonists</subject><subject>Proteolipids</subject><subject>Receptors, Lipoprotein - genetics</subject><subject>Receptors, Lipoprotein - metabolism</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Scavenger Receptors, Class B - genetics</subject><subject>Scavenger Receptors, Class B - metabolism</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Transcription, Genetic - drug effects</subject><subject>Up-Regulation</subject><issn>1087-0571</issn><issn>2472-5552</issn><issn>1552-454X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGL1DAUxoso7rp69yQ5eeuatH1Nexxn1VkYFHQHvJU36UsnS5vUpBXm5p9uSgcEQSSH5OX9vo-XfEnyWvBbIaR8J3glOUjBy6yWUFZPkmsBkKUFFN-fxnNsp0v_KnkRwiPnIi958Ty5EjKDGmpxnfy6b8lORhuFk3GWOc0-u5_Us908oGU7053SO7LBTGe2N6MbvZvIWPaVFI2T8-wwpp66ucdYBHYIxnYM2Zb6Pn2PgdrV4uHk3dydxnli35Qnsgu2CQHPL5NnGvtAry77TXL4-OFhu0v3Xz7dbzf7VIHIpxQ0oNCZEAqQo8qgzbQUVQ7QKoIyVyh1JUDVVGTtUZcyqjSiKsSxKjVCfpO8XX3jC37MFKZmMEHFMdGSm0MjeQZQ19V_wUzEKUq-ON6uYIc9NcZqN3lUcbU0GOUsaRPvN5GVAupiEfBVoLwLwZNuRm8G9OdG8GbJs_k7zyh5cxlmPg7U_hFcAoxAugIBO2oe3ext_MV_G_4Gm7uo1Q</recordid><startdate>200703</startdate><enddate>200703</enddate><creator>Yang, Yuan</creator><creator>Zhang, Zhongbing</creator><creator>Jiang, Wei</creator><creator>Gao, Lei</creator><creator>Zhao, Guiyu</creator><creator>Zheng, Zhihui</creator><creator>Wang, Min</creator><creator>Si, Shuyi</creator><creator>Hong, Bin</creator><general>Sage Publications</general><general>Sage Publications, Inc</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200703</creationdate><title>Identification of Novel Human High-Density Lipoprotein Receptor Up-regulators Using a Cell-Based High-Throughput Screening Assay</title><author>Yang, Yuan ; Zhang, Zhongbing ; Jiang, Wei ; Gao, Lei ; Zhao, Guiyu ; Zheng, Zhihui ; Wang, Min ; Si, Shuyi ; Hong, Bin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-5f5a1f211c5a0ac25d2f718355dce563ca7f815c9e42dbf67513faac41b86fa53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Actinomycetaceae - metabolism</topic><topic>Actinomycetes</topic><topic>Atherosclerosis</topic><topic>Biological Assay - methods</topic><topic>Blood lipoproteins</topic><topic>Carbocyanines</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical</topic><topic>Fermentation</topic><topic>Fluorescent Dyes</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Hydroxyl Radical - chemistry</topic><topic>Isoflavones - isolation & purification</topic><topic>Isoflavones - pharmacology</topic><topic>Lipoproteins</topic><topic>Lipoproteins, HDL - genetics</topic><topic>Lipoproteins, HDL - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Luciferases - metabolism</topic><topic>Metabolites</topic><topic>PPAR gamma - agonists</topic><topic>Proteolipids</topic><topic>Receptors, Lipoprotein - genetics</topic><topic>Receptors, Lipoprotein - metabolism</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Scavenger Receptors, Class B - genetics</topic><topic>Scavenger Receptors, Class B - metabolism</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Transcription, Genetic - drug effects</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yuan</creatorcontrib><creatorcontrib>Zhang, Zhongbing</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><creatorcontrib>Zhao, Guiyu</creatorcontrib><creatorcontrib>Zheng, Zhihui</creatorcontrib><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Si, Shuyi</creatorcontrib><creatorcontrib>Hong, Bin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomolecular screening</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Yuan</au><au>Zhang, Zhongbing</au><au>Jiang, Wei</au><au>Gao, Lei</au><au>Zhao, Guiyu</au><au>Zheng, Zhihui</au><au>Wang, Min</au><au>Si, Shuyi</au><au>Hong, Bin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Novel Human High-Density Lipoprotein Receptor Up-regulators Using a Cell-Based High-Throughput Screening Assay</atitle><jtitle>Journal of biomolecular screening</jtitle><addtitle>J Biomol Screen</addtitle><date>2007-03</date><risdate>2007</risdate><volume>12</volume><issue>2</issue><spage>211</spage><epage>219</epage><pages>211-219</pages><issn>1087-0571</issn><issn>2472-5552</issn><eissn>1552-454X</eissn><abstract>Scavenger receptor class B type I (SR-BI) is the high-affinity high-density lipoprotein (HDL) receptor, and CLA-1 is the human homologue of the murine SR-BI. CLA-1/SR-BI receptor has been suggested as a new preventative and/or therapeutic target for atherosclerosis due to its pivotal role in overall HDL cholesterol (HDL-C) metabolism and its antiatherogenic activity in vivo. To search for active compounds that can increase CLA-1 transcription, a novel cell-based assay was developed for application in high-throughput screening (HTS). Human hepatoma HepG2 cells were transfected with a CLA-1-promoter-luciferase reporter gene construct, and the stable transfected cell line was selected and named CLAp-LUC HepG2. With rosiglitazone as a positive control, this stable cell line was used to establish a specific CLA-1 gene expression assay in a 96-well microplate format. The evaluating parameter Z' value of 0.64 showed that this cell-based HTS assay was robust and reliable. Screening of 6000 microbial secondary metabolite crude extracts identified 8 positive strains. Between 2 identified CLA-1 up-regulators produced by actinomycete strain 04-4776, 4776B may stimulate not only the expression of CLA-1 on the transcriptional and translational levels but also the activity of CLA-1 to uptake the HDL-C in HepG2 cells. The active compounds originated from this HTS assay may be developed to drug candidates or lead compounds for new antiatherosclerosis agents.</abstract><cop>Thousand Oaks, CA</cop><pub>Sage Publications</pub><pmid>17259591</pmid><doi>10.1177/1087057106297568</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actinomycetaceae - metabolism Actinomycetes Atherosclerosis Biological Assay - methods Blood lipoproteins Carbocyanines Carcinoma, Hepatocellular - pathology Cell Line, Tumor Dose-Response Relationship, Drug Drug Evaluation, Preclinical Fermentation Fluorescent Dyes Gene Expression Regulation - drug effects Genes, Reporter Humans Hydroxyl Radical - chemistry Isoflavones - isolation & purification Isoflavones - pharmacology Lipoproteins Lipoproteins, HDL - genetics Lipoproteins, HDL - metabolism Liver Neoplasms - pathology Luciferases - metabolism Metabolites PPAR gamma - agonists Proteolipids Receptors, Lipoprotein - genetics Receptors, Lipoprotein - metabolism Recombinant Fusion Proteins - metabolism Scavenger Receptors, Class B - genetics Scavenger Receptors, Class B - metabolism Thiazolidinediones - pharmacology Transcription, Genetic - drug effects Up-Regulation |
| title | Identification of Novel Human High-Density Lipoprotein Receptor Up-regulators Using a Cell-Based High-Throughput Screening Assay |
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