Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response
The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity and mRNA levels of serine palmitoyltransferase, the...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 1999-07, Vol.274 (28), p.19707-19713 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 19713 |
|---|---|
| container_issue | 28 |
| container_start_page | 19707 |
| container_title | The Journal of biological chemistry |
| container_volume | 274 |
| creator | Memon, R A Holleran, W M Uchida, Y Moser, A H Ichikawa, S Hirabayashi, Y Grunfeld, C Feingold, K R |
| description | The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown
recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity
and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content
of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced
increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the
effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase,
the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer
synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer
synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3â4-fold increase in hepatic
GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction)
as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover,
both tumor necrosis factor-α and interleukin-1β, cytokines that mediate many of the metabolic effects of LPS, increased hepatic
GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro , suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and
cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro . An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account
for the increased GlcCer content in circulating lipoproteins during the acute phase response. |
| doi_str_mv | 10.1074/jbc.274.28.19707 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17273302</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17273302</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-4f2bafb193ba0b3c54d49cc16c991388d25e3717b696fd67e12749587fe18d3</originalsourceid><addsrcrecordid>eNpVkE1P3DAQhq2qqLt83DkhH1BvWTx2EsfHFaKAtFURcOBmxc5kY5TEIU6o-PcYwqGdy8zheV9pHkJOgW2AyfTi2dgNl-mGFxtQkslvZA2sEInI4Ok7WTPGIVE8K1bkMIRnFidV8IOsgAkFCmBNHu5xP7fl5HxPfU2v2zfrw9C4fu9bN7iK_sapNPEOHXU93blXHGk1jxGgU4N0a-cJ6V1TBqT3GAbfBzwmB3XZBjz52kfk4dfV4-VNsvtzfXu53SU2zcWUpDU3ZW1ACVMyI2yWVqmyFnKrFIiiqHiGQoI0ucrrKpcI8VWVFbJGKCpxRH4urcPoX2YMk-5csNi2ZY9-Dhokl0IwHkG2gHb0IYxY62F0XTm-aWD6Q6OOGnXs1rzQnxpj5OyrezYdVv8EFm8ROF-Axu2bv25EbZy3DXb_97wD6T56TQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17273302</pqid></control><display><type>article</type><title>Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Memon, R A ; Holleran, W M ; Uchida, Y ; Moser, A H ; Ichikawa, S ; Hirabayashi, Y ; Grunfeld, C ; Feingold, K R</creator><creatorcontrib>Memon, R A ; Holleran, W M ; Uchida, Y ; Moser, A H ; Ichikawa, S ; Hirabayashi, Y ; Grunfeld, C ; Feingold, K R</creatorcontrib><description>The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown
recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity
and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content
of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced
increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the
effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase,
the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer
synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer
synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3â4-fold increase in hepatic
GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction)
as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover,
both tumor necrosis factor-α and interleukin-1β, cytokines that mediate many of the metabolic effects of LPS, increased hepatic
GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro , suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and
cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro . An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account
for the increased GlcCer content in circulating lipoproteins during the acute phase response.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.274.28.19707</identifier><identifier>PMID: 10391911</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Acute-Phase Reaction - chemically induced ; Acute-Phase Reaction - metabolism ; Animals ; Cricetinae ; Gene Expression Regulation, Enzymologic - drug effects ; Glucosylceramides - metabolism ; Glucosyltransferases - genetics ; Glycosphingolipids - metabolism ; Interleukin-1 - pharmacology ; Interleukin-6 - pharmacology ; Lipopolysaccharides ; Liver - metabolism ; Male ; Mesocricetus ; RNA, Messenger - metabolism ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 1999-07, Vol.274 (28), p.19707-19713</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-4f2bafb193ba0b3c54d49cc16c991388d25e3717b696fd67e12749587fe18d3</citedby><cites>FETCH-LOGICAL-c463t-4f2bafb193ba0b3c54d49cc16c991388d25e3717b696fd67e12749587fe18d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10391911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Memon, R A</creatorcontrib><creatorcontrib>Holleran, W M</creatorcontrib><creatorcontrib>Uchida, Y</creatorcontrib><creatorcontrib>Moser, A H</creatorcontrib><creatorcontrib>Ichikawa, S</creatorcontrib><creatorcontrib>Hirabayashi, Y</creatorcontrib><creatorcontrib>Grunfeld, C</creatorcontrib><creatorcontrib>Feingold, K R</creatorcontrib><title>Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown
recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity
and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content
of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced
increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the
effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase,
the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer
synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer
synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3â4-fold increase in hepatic
GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction)
as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover,
both tumor necrosis factor-α and interleukin-1β, cytokines that mediate many of the metabolic effects of LPS, increased hepatic
GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro , suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and
cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro . An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account
for the increased GlcCer content in circulating lipoproteins during the acute phase response.</description><subject>Acute-Phase Reaction - chemically induced</subject><subject>Acute-Phase Reaction - metabolism</subject><subject>Animals</subject><subject>Cricetinae</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Glucosylceramides - metabolism</subject><subject>Glucosyltransferases - genetics</subject><subject>Glycosphingolipids - metabolism</subject><subject>Interleukin-1 - pharmacology</subject><subject>Interleukin-6 - pharmacology</subject><subject>Lipopolysaccharides</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mesocricetus</subject><subject>RNA, Messenger - metabolism</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1P3DAQhq2qqLt83DkhH1BvWTx2EsfHFaKAtFURcOBmxc5kY5TEIU6o-PcYwqGdy8zheV9pHkJOgW2AyfTi2dgNl-mGFxtQkslvZA2sEInI4Ok7WTPGIVE8K1bkMIRnFidV8IOsgAkFCmBNHu5xP7fl5HxPfU2v2zfrw9C4fu9bN7iK_sapNPEOHXU93blXHGk1jxGgU4N0a-cJ6V1TBqT3GAbfBzwmB3XZBjz52kfk4dfV4-VNsvtzfXu53SU2zcWUpDU3ZW1ACVMyI2yWVqmyFnKrFIiiqHiGQoI0ucrrKpcI8VWVFbJGKCpxRH4urcPoX2YMk-5csNi2ZY9-Dhokl0IwHkG2gHb0IYxY62F0XTm-aWD6Q6OOGnXs1rzQnxpj5OyrezYdVv8EFm8ROF-Axu2bv25EbZy3DXb_97wD6T56TQ</recordid><startdate>19990709</startdate><enddate>19990709</enddate><creator>Memon, R A</creator><creator>Holleran, W M</creator><creator>Uchida, Y</creator><creator>Moser, A H</creator><creator>Ichikawa, S</creator><creator>Hirabayashi, Y</creator><creator>Grunfeld, C</creator><creator>Feingold, K R</creator><general>American Society for Biochemistry and Molecular Biology</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>7TM</scope></search><sort><creationdate>19990709</creationdate><title>Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response</title><author>Memon, R A ; Holleran, W M ; Uchida, Y ; Moser, A H ; Ichikawa, S ; Hirabayashi, Y ; Grunfeld, C ; Feingold, K R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-4f2bafb193ba0b3c54d49cc16c991388d25e3717b696fd67e12749587fe18d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Acute-Phase Reaction - chemically induced</topic><topic>Acute-Phase Reaction - metabolism</topic><topic>Animals</topic><topic>Cricetinae</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Glucosylceramides - metabolism</topic><topic>Glucosyltransferases - genetics</topic><topic>Glycosphingolipids - metabolism</topic><topic>Interleukin-1 - pharmacology</topic><topic>Interleukin-6 - pharmacology</topic><topic>Lipopolysaccharides</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mesocricetus</topic><topic>RNA, Messenger - metabolism</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Memon, R A</creatorcontrib><creatorcontrib>Holleran, W M</creatorcontrib><creatorcontrib>Uchida, Y</creatorcontrib><creatorcontrib>Moser, A H</creatorcontrib><creatorcontrib>Ichikawa, S</creatorcontrib><creatorcontrib>Hirabayashi, Y</creatorcontrib><creatorcontrib>Grunfeld, C</creatorcontrib><creatorcontrib>Feingold, K 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>Nucleic Acids Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Memon, R A</au><au>Holleran, W M</au><au>Uchida, Y</au><au>Moser, A H</au><au>Ichikawa, S</au><au>Hirabayashi, Y</au><au>Grunfeld, C</au><au>Feingold, K R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1999-07-09</date><risdate>1999</risdate><volume>274</volume><issue>28</issue><spage>19707</spage><epage>19713</epage><pages>19707-19713</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown
recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity
and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content
of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced
increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the
effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase,
the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer
synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer
synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3â4-fold increase in hepatic
GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction)
as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover,
both tumor necrosis factor-α and interleukin-1β, cytokines that mediate many of the metabolic effects of LPS, increased hepatic
GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro , suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and
cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro . An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account
for the increased GlcCer content in circulating lipoproteins during the acute phase response.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>10391911</pmid><doi>10.1074/jbc.274.28.19707</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1999-07, Vol.274 (28), p.19707-19713 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17273302 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Acute-Phase Reaction - chemically induced Acute-Phase Reaction - metabolism Animals Cricetinae Gene Expression Regulation, Enzymologic - drug effects Glucosylceramides - metabolism Glucosyltransferases - genetics Glycosphingolipids - metabolism Interleukin-1 - pharmacology Interleukin-6 - pharmacology Lipopolysaccharides Liver - metabolism Male Mesocricetus RNA, Messenger - metabolism Tumor Cells, Cultured |
| title | Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T17%3A54%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Regulation%20of%20Glycosphingolipid%20Metabolism%20in%20Liver%20during%20the%20Acute%20Phase%20Response&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Memon,%20R%20A&rft.date=1999-07-09&rft.volume=274&rft.issue=28&rft.spage=19707&rft.epage=19713&rft.pages=19707-19713&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.274.28.19707&rft_dat=%3Cproquest_cross%3E17273302%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17273302&rft_id=info:pmid/10391911&rfr_iscdi=true |