Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase
Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis prod...
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| Veröffentlicht in: | Lipids 2017-03, Vol.52 (3), p.189-205 |
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| creator | Thyagarajan, Narmadaa Marshall, Jenika D. Pickett, Arthur T. Schumacher, Clemens Yang, Yanbo Christian, Sherri L. Brown, Robert J. |
| description | Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression of
SNORA56
, as well as the expression of genes associated with the cell cycle (
PCNA
and
DKC1
variant 3), stress response (
ATF3
), type I interferon signaling (
IFITM1
), and lipid metabolism (
CD36
and
PLIN2
) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA. |
| doi_str_mv | 10.1007/s11745-017-4238-1 |
| format | Article |
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SNORA56
, as well as the expression of genes associated with the cell cycle (
PCNA
and
DKC1
variant 3), stress response (
ATF3
), type I interferon signaling (
IFITM1
), and lipid metabolism (
CD36
and
PLIN2
) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.</description><identifier>ISSN: 0024-4201</identifier><identifier>EISSN: 1558-9307</identifier><identifier>DOI: 10.1007/s11745-017-4238-1</identifier><identifier>PMID: 28205069</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Atherosclerosis ; Bioinformatics ; Biomedical and Life Sciences ; Cell Cycle Proteins - genetics ; Cell Line ; Cholesterol - pharmacology ; Fatty acids ; Fatty Acids, Nonesterified - pharmacology ; Foam Cells - drug effects ; Foam Cells - metabolism ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation - drug effects ; Humans ; Hydrolysis ; Life Sciences ; Lipid Metabolism ; Lipidology ; Lipoprotein lipase ; Lipoprotein Lipase - metabolism ; Lipoproteins ; Lipoproteins - chemistry ; Lipoproteins - pharmacology ; Macrophages - drug effects ; Macrophages - metabolism ; Medical Biochemistry ; Medicinal Chemistry ; Microarray analysis ; Microbial Genetics and Genomics ; Molecular biology ; Neurochemistry ; Nutrition ; Oligonucleotide Array Sequence Analysis - methods ; Original Article ; RNA, Small Nucleolar - genetics ; Signal Transduction ; Small nucleolar RNA ; Triglycerides - pharmacology</subject><ispartof>Lipids, 2017-03, Vol.52 (3), p.189-205</ispartof><rights>AOCS 2017</rights><rights>2017 American Oil Chemists' Society (AOCS)</rights><rights>Lipids is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4209-af52427f65fbfaa92dd3987702c0ffb6e38d2aca31bed3a63eb68fa5689091703</citedby><cites>FETCH-LOGICAL-c4209-af52427f65fbfaa92dd3987702c0ffb6e38d2aca31bed3a63eb68fa5689091703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11745-017-4238-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11745-017-4238-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,41488,42557,45574,45575,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28205069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thyagarajan, Narmadaa</creatorcontrib><creatorcontrib>Marshall, Jenika D.</creatorcontrib><creatorcontrib>Pickett, Arthur T.</creatorcontrib><creatorcontrib>Schumacher, Clemens</creatorcontrib><creatorcontrib>Yang, Yanbo</creatorcontrib><creatorcontrib>Christian, Sherri L.</creatorcontrib><creatorcontrib>Brown, Robert J.</creatorcontrib><title>Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase</title><title>Lipids</title><addtitle>Lipids</addtitle><addtitle>Lipids</addtitle><description>Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression of
SNORA56
, as well as the expression of genes associated with the cell cycle (
PCNA
and
DKC1
variant 3), stress response (
ATF3
), type I interferon signaling (
IFITM1
), and lipid metabolism (
CD36
and
PLIN2
) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.</description><subject>Atherosclerosis</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Line</subject><subject>Cholesterol - pharmacology</subject><subject>Fatty acids</subject><subject>Fatty Acids, Nonesterified - pharmacology</subject><subject>Foam Cells - drug effects</subject><subject>Foam Cells - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Life Sciences</subject><subject>Lipid Metabolism</subject><subject>Lipidology</subject><subject>Lipoprotein lipase</subject><subject>Lipoprotein Lipase - metabolism</subject><subject>Lipoproteins</subject><subject>Lipoproteins - chemistry</subject><subject>Lipoproteins - pharmacology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Medical Biochemistry</subject><subject>Medicinal Chemistry</subject><subject>Microarray analysis</subject><subject>Microbial Genetics and Genomics</subject><subject>Molecular biology</subject><subject>Neurochemistry</subject><subject>Nutrition</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Original Article</subject><subject>RNA, Small Nucleolar - genetics</subject><subject>Signal Transduction</subject><subject>Small nucleolar RNA</subject><subject>Triglycerides - pharmacology</subject><issn>0024-4201</issn><issn>1558-9307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNqFkUFv1DAQhS0EokvLD-CCLHHhEvDYSWwfq7Z0Ky1iD9uz5STjkiobBztRyb_HUQqCSqgn2_L33jzNI-QdsE_AmPwcAWReZAxklnOhMnhBNlAUKtOCyZdkwxjP0w-DE_Imxvv0hFwXr8kJV5wVrNQb8nAIto91aIfRH9uanve2m2MbqXf0sN1nQL_aOvjhu73DSK9-Dj5iQ0dPd-3gh-BHbHu6nZvgV9k--Gaqx0ivscdgxwRX8z9wutuIZ-SVs13Et4_nKbn9cnW42Ga7b9c3F-e7rE65dWZdwXMuXVm4ylmredMIraRkvGbOVSUK1XBbWwEVNsKWAqtSOVuUSjMNkolT8nH1TeN_TBhHc2xjjV1ne_RTNKBKzUqR1pHQD0_Qez-FtI-FkiATpRZDWKm0lRgDOjOE9mjDbICZpRWztmJSK2ZpxUDSvH90nqojNn8Uv2tIgFyBh7bD-XlHs7vZXzJQi5KvyphE_R2Gv0L_N88ve3eo5A</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Thyagarajan, Narmadaa</creator><creator>Marshall, Jenika D.</creator><creator>Pickett, Arthur T.</creator><creator>Schumacher, Clemens</creator><creator>Yang, Yanbo</creator><creator>Christian, Sherri L.</creator><creator>Brown, Robert J.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</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>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>201703</creationdate><title>Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase</title><author>Thyagarajan, Narmadaa ; Marshall, Jenika D. ; Pickett, Arthur T. ; Schumacher, Clemens ; Yang, Yanbo ; Christian, Sherri L. ; Brown, Robert J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4209-af52427f65fbfaa92dd3987702c0ffb6e38d2aca31bed3a63eb68fa5689091703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Atherosclerosis</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Line</topic><topic>Cholesterol - pharmacology</topic><topic>Fatty acids</topic><topic>Fatty Acids, Nonesterified - pharmacology</topic><topic>Foam Cells - drug effects</topic><topic>Foam Cells - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Life Sciences</topic><topic>Lipid Metabolism</topic><topic>Lipidology</topic><topic>Lipoprotein lipase</topic><topic>Lipoprotein Lipase - metabolism</topic><topic>Lipoproteins</topic><topic>Lipoproteins - chemistry</topic><topic>Lipoproteins - pharmacology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Medical Biochemistry</topic><topic>Medicinal Chemistry</topic><topic>Microarray analysis</topic><topic>Microbial Genetics and Genomics</topic><topic>Molecular biology</topic><topic>Neurochemistry</topic><topic>Nutrition</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Original Article</topic><topic>RNA, Small Nucleolar - genetics</topic><topic>Signal Transduction</topic><topic>Small nucleolar RNA</topic><topic>Triglycerides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thyagarajan, Narmadaa</creatorcontrib><creatorcontrib>Marshall, Jenika D.</creatorcontrib><creatorcontrib>Pickett, Arthur T.</creatorcontrib><creatorcontrib>Schumacher, Clemens</creatorcontrib><creatorcontrib>Yang, Yanbo</creatorcontrib><creatorcontrib>Christian, Sherri L.</creatorcontrib><creatorcontrib>Brown, Robert J.</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</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>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</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>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic 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>MEDLINE - Academic</collection><jtitle>Lipids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thyagarajan, Narmadaa</au><au>Marshall, Jenika D.</au><au>Pickett, Arthur T.</au><au>Schumacher, Clemens</au><au>Yang, Yanbo</au><au>Christian, Sherri L.</au><au>Brown, Robert J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase</atitle><jtitle>Lipids</jtitle><stitle>Lipids</stitle><addtitle>Lipids</addtitle><date>2017-03</date><risdate>2017</risdate><volume>52</volume><issue>3</issue><spage>189</spage><epage>205</epage><pages>189-205</pages><issn>0024-4201</issn><eissn>1558-9307</eissn><abstract>Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression of
SNORA56
, as well as the expression of genes associated with the cell cycle (
PCNA
and
DKC1
variant 3), stress response (
ATF3
), type I interferon signaling (
IFITM1
), and lipid metabolism (
CD36
and
PLIN2
) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28205069</pmid><doi>10.1007/s11745-017-4238-1</doi><tpages>17</tpages></addata></record> |
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| ispartof | Lipids, 2017-03, Vol.52 (3), p.189-205 |
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| language | eng |
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| subjects | Atherosclerosis Bioinformatics Biomedical and Life Sciences Cell Cycle Proteins - genetics Cell Line Cholesterol - pharmacology Fatty acids Fatty Acids, Nonesterified - pharmacology Foam Cells - drug effects Foam Cells - metabolism Gene expression Gene Expression Profiling - methods Gene Expression Regulation - drug effects Humans Hydrolysis Life Sciences Lipid Metabolism Lipidology Lipoprotein lipase Lipoprotein Lipase - metabolism Lipoproteins Lipoproteins - chemistry Lipoproteins - pharmacology Macrophages - drug effects Macrophages - metabolism Medical Biochemistry Medicinal Chemistry Microarray analysis Microbial Genetics and Genomics Molecular biology Neurochemistry Nutrition Oligonucleotide Array Sequence Analysis - methods Original Article RNA, Small Nucleolar - genetics Signal Transduction Small nucleolar RNA Triglycerides - pharmacology |
| title | Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase |
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