Enhanced Expression of Osteopontin by High Glucose: Involvement of Osteopontin in Diabetic Macroangiopathy
Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cell...
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| Veröffentlicht in: | Annals of the New York Academy of Sciences 2000-05, Vol.902 (1), p.357-363 |
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| creator | TAKEMOTO, MINORU YOKOTE, KOUTARO YAMAZAKI, MASASHI RIDALL, AMY L. BUTLER, WILLIAM T. MATSUMOTO, TARO TAMURA, KEN SAITO, YASUSHI MORI, SEIJIRO |
| description | Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications. |
| doi_str_mv | 10.1111/j.1749-6632.2000.tb06338.x |
| format | Article |
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Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.</description><identifier>ISSN: 0077-8923</identifier><identifier>EISSN: 1749-6632</identifier><identifier>DOI: 10.1111/j.1749-6632.2000.tb06338.x</identifier><identifier>PMID: 10865863</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Aorta ; Arteriosclerosis - physiopathology ; Cell Adhesion ; Cells, Cultured ; Diabetic Angiopathies - physiopathology ; Enzyme Activation - drug effects ; Enzyme Inhibitors - pharmacology ; Gene Expression Regulation - drug effects ; Glucose - pharmacology ; Indoles - pharmacology ; Maleimides - pharmacology ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; Osteopontin ; Promoter Regions, Genetic ; Protein Kinase C - metabolism ; Rats ; RNA, Messenger - genetics ; Sialoglycoproteins - genetics ; Transcription, Genetic</subject><ispartof>Annals of the New York Academy of Sciences, 2000-05, Vol.902 (1), p.357-363</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-58ac096510ae08206b6b4f09e7d2c2e9844aa30699d42d498bde27c709f705673</citedby><cites>FETCH-LOGICAL-c353t-58ac096510ae08206b6b4f09e7d2c2e9844aa30699d42d498bde27c709f705673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10865863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TAKEMOTO, MINORU</creatorcontrib><creatorcontrib>YOKOTE, KOUTARO</creatorcontrib><creatorcontrib>YAMAZAKI, MASASHI</creatorcontrib><creatorcontrib>RIDALL, AMY L.</creatorcontrib><creatorcontrib>BUTLER, WILLIAM T.</creatorcontrib><creatorcontrib>MATSUMOTO, TARO</creatorcontrib><creatorcontrib>TAMURA, KEN</creatorcontrib><creatorcontrib>SAITO, YASUSHI</creatorcontrib><creatorcontrib>MORI, SEIJIRO</creatorcontrib><title>Enhanced Expression of Osteopontin by High Glucose: Involvement of Osteopontin in Diabetic Macroangiopathy</title><title>Annals of the New York Academy of Sciences</title><addtitle>Ann N Y Acad Sci</addtitle><description>Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.</description><subject>Animals</subject><subject>Aorta</subject><subject>Arteriosclerosis - physiopathology</subject><subject>Cell Adhesion</subject><subject>Cells, Cultured</subject><subject>Diabetic Angiopathies - physiopathology</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucose - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Maleimides - pharmacology</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Osteopontin</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Kinase C - metabolism</subject><subject>Rats</subject><subject>RNA, Messenger - genetics</subject><subject>Sialoglycoproteins - genetics</subject><subject>Transcription, Genetic</subject><issn>0077-8923</issn><issn>1749-6632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkEtv1DAQgC0EokvhL6CIA7ekYzvxozfULttWLeUA4mg5zqTrJWuHOFvt_nsS7apCjEaaw3zz0EfIJwoFneJiU1BZ6lwIzgoGAMVYg-BcFftXZPHSek0WAFLmSjN-Rt6ltAGgTJXyLTmjoESlBF-QzTKsbXDYZMt9P2BKPoYsttljGjH2MYw-ZPUhu_FP62zV7VxMeJndhufYPeMWw_g_O-W1tzWO3mUP1g3RhicfezuuD-_Jm9Z2CT-c6jn5-XX54-omv39c3V59uc8dr_iYV8o60KKiYBEUA1GLumxBo2yYY6hVWVrLQWjdlKwptaobZNJJ0K2ESkh-Tj4f9_ZD_LPDNJqtTw67zgaMu2QkZaConMHLIzi9mdKArekHv7XDwVAws2mzMbNOM-s0s2lzMm320_DH05VdvcXmn9Gj2gnIj4Cf9Oxf-nb4baYnZWV-fVuZ79f04Q6YMsD_Av0tiyY</recordid><startdate>200005</startdate><enddate>200005</enddate><creator>TAKEMOTO, MINORU</creator><creator>YOKOTE, KOUTARO</creator><creator>YAMAZAKI, MASASHI</creator><creator>RIDALL, AMY L.</creator><creator>BUTLER, WILLIAM T.</creator><creator>MATSUMOTO, TARO</creator><creator>TAMURA, KEN</creator><creator>SAITO, YASUSHI</creator><creator>MORI, SEIJIRO</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>200005</creationdate><title>Enhanced Expression of Osteopontin by High Glucose: Involvement of Osteopontin in Diabetic Macroangiopathy</title><author>TAKEMOTO, MINORU ; YOKOTE, KOUTARO ; YAMAZAKI, MASASHI ; RIDALL, AMY L. ; BUTLER, WILLIAM T. ; MATSUMOTO, TARO ; TAMURA, KEN ; SAITO, YASUSHI ; MORI, SEIJIRO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-58ac096510ae08206b6b4f09e7d2c2e9844aa30699d42d498bde27c709f705673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Aorta</topic><topic>Arteriosclerosis - physiopathology</topic><topic>Cell Adhesion</topic><topic>Cells, Cultured</topic><topic>Diabetic Angiopathies - physiopathology</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucose - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Maleimides - pharmacology</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Osteopontin</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Kinase C - metabolism</topic><topic>Rats</topic><topic>RNA, Messenger - genetics</topic><topic>Sialoglycoproteins - genetics</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TAKEMOTO, MINORU</creatorcontrib><creatorcontrib>YOKOTE, KOUTARO</creatorcontrib><creatorcontrib>YAMAZAKI, MASASHI</creatorcontrib><creatorcontrib>RIDALL, AMY L.</creatorcontrib><creatorcontrib>BUTLER, WILLIAM T.</creatorcontrib><creatorcontrib>MATSUMOTO, TARO</creatorcontrib><creatorcontrib>TAMURA, KEN</creatorcontrib><creatorcontrib>SAITO, YASUSHI</creatorcontrib><creatorcontrib>MORI, SEIJIRO</creatorcontrib><collection>Istex</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>Annals of the New York Academy of Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TAKEMOTO, MINORU</au><au>YOKOTE, KOUTARO</au><au>YAMAZAKI, MASASHI</au><au>RIDALL, AMY L.</au><au>BUTLER, WILLIAM T.</au><au>MATSUMOTO, TARO</au><au>TAMURA, KEN</au><au>SAITO, YASUSHI</au><au>MORI, SEIJIRO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced Expression of Osteopontin by High Glucose: Involvement of Osteopontin in Diabetic Macroangiopathy</atitle><jtitle>Annals of the New York Academy of Sciences</jtitle><addtitle>Ann N Y Acad Sci</addtitle><date>2000-05</date><risdate>2000</risdate><volume>902</volume><issue>1</issue><spage>357</spage><epage>363</epage><pages>357-363</pages><issn>0077-8923</issn><eissn>1749-6632</eissn><abstract>Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10865863</pmid><doi>10.1111/j.1749-6632.2000.tb06338.x</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Aorta Arteriosclerosis - physiopathology Cell Adhesion Cells, Cultured Diabetic Angiopathies - physiopathology Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Gene Expression Regulation - drug effects Glucose - pharmacology Indoles - pharmacology Maleimides - pharmacology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology Osteopontin Promoter Regions, Genetic Protein Kinase C - metabolism Rats RNA, Messenger - genetics Sialoglycoproteins - genetics Transcription, Genetic |
| title | Enhanced Expression of Osteopontin by High Glucose: Involvement of Osteopontin in Diabetic Macroangiopathy |
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