Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis
•IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression. We elucidated the molecular mechanism of prostaglandin (...
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| Veröffentlicht in: | Molecular and cellular endocrinology 2014-03, Vol.384 (1-2), p.12-22 |
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| creator | Fujimori, Ko Yano, Mutsumi Miyake, Haruka Kimura, Hiroko |
| description | •IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression.
We elucidated the molecular mechanism of prostaglandin (PG) E2- and PGF2α-mediated suppression of the early phase of adipogenesis through enhanced COX-2 expression in 3T3-L1 cells. 3-Isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase which catalyzes the conversion of cAMP to AMP, enhanced the activity of protein kinase A (PKA). Dibutyryl cAMP activated PKA and enhanced the phosphorylation of cAMP response element (CRE)-binding protein (CREB). The ability of CREB binding to the CRE of the COX-2 promoter was elevated for enhancement of the expression of the COX-2 gene. CREB siRNA suppressed the expression of the COX-2 gene. Furthermore, okadaic acid, a protein phosphatase (PP) 1/2A inhibitor, suppressed the progression of adipogenesis by preventing PP1/2A-mediated suppression of CREB-dependent COX-2 expression, thus resulting in increased production of anti-adipogenic PGE2 and PGF2α. These results indicate that CREB-dependent expression of COX-2 for the production of anti-adipogenic PGs is critical for the regulation of the early phase of adipogenesis. |
| doi_str_mv | 10.1016/j.mce.2013.12.014 |
| format | Article |
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We elucidated the molecular mechanism of prostaglandin (PG) E2- and PGF2α-mediated suppression of the early phase of adipogenesis through enhanced COX-2 expression in 3T3-L1 cells. 3-Isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase which catalyzes the conversion of cAMP to AMP, enhanced the activity of protein kinase A (PKA). Dibutyryl cAMP activated PKA and enhanced the phosphorylation of cAMP response element (CRE)-binding protein (CREB). The ability of CREB binding to the CRE of the COX-2 promoter was elevated for enhancement of the expression of the COX-2 gene. CREB siRNA suppressed the expression of the COX-2 gene. Furthermore, okadaic acid, a protein phosphatase (PP) 1/2A inhibitor, suppressed the progression of adipogenesis by preventing PP1/2A-mediated suppression of CREB-dependent COX-2 expression, thus resulting in increased production of anti-adipogenic PGE2 and PGF2α. These results indicate that CREB-dependent expression of COX-2 for the production of anti-adipogenic PGs is critical for the regulation of the early phase of adipogenesis.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2013.12.014</identifier><identifier>PMID: 24378735</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>1-Methyl-3-isobutylxanthine - pharmacology ; 3T3-L1 Cells ; Adipocytes ; Adipocytes - cytology ; Adipocytes - drug effects ; Adipocytes - metabolism ; Adipogenesis - genetics ; Animals ; Bucladesine - pharmacology ; Cell Differentiation ; COX-2 ; CREB ; CREB-Binding Protein - antagonists & inhibitors ; CREB-Binding Protein - genetics ; CREB-Binding Protein - metabolism ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - metabolism ; Dinoprostone - biosynthesis ; Gene Expression Regulation ; Mice ; Okadaic Acid - pharmacology ; Phosphoric Diester Hydrolases - genetics ; Phosphoric Diester Hydrolases - metabolism ; PKA ; PP1/2A ; Promoter Regions, Genetic ; Prostaglandin ; Protein Binding ; Protein Phosphatase 1 - antagonists & inhibitors ; Protein Phosphatase 1 - genetics ; Protein Phosphatase 1 - metabolism ; Protein Phosphatase 2 - antagonists & inhibitors ; Protein Phosphatase 2 - genetics ; Protein Phosphatase 2 - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Signal Transduction</subject><ispartof>Molecular and cellular endocrinology, 2014-03, Vol.384 (1-2), p.12-22</ispartof><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-8ebaee7831cbbd5d1a0bd160d5e8e590c85028415e2795d61610f93904aec5363</citedby><cites>FETCH-LOGICAL-c419t-8ebaee7831cbbd5d1a0bd160d5e8e590c85028415e2795d61610f93904aec5363</cites><orcidid>0000-0002-2506-0769</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2013.12.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24378735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujimori, Ko</creatorcontrib><creatorcontrib>Yano, Mutsumi</creatorcontrib><creatorcontrib>Miyake, Haruka</creatorcontrib><creatorcontrib>Kimura, Hiroko</creatorcontrib><title>Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>•IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression.
We elucidated the molecular mechanism of prostaglandin (PG) E2- and PGF2α-mediated suppression of the early phase of adipogenesis through enhanced COX-2 expression in 3T3-L1 cells. 3-Isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase which catalyzes the conversion of cAMP to AMP, enhanced the activity of protein kinase A (PKA). Dibutyryl cAMP activated PKA and enhanced the phosphorylation of cAMP response element (CRE)-binding protein (CREB). The ability of CREB binding to the CRE of the COX-2 promoter was elevated for enhancement of the expression of the COX-2 gene. CREB siRNA suppressed the expression of the COX-2 gene. Furthermore, okadaic acid, a protein phosphatase (PP) 1/2A inhibitor, suppressed the progression of adipogenesis by preventing PP1/2A-mediated suppression of CREB-dependent COX-2 expression, thus resulting in increased production of anti-adipogenic PGE2 and PGF2α. These results indicate that CREB-dependent expression of COX-2 for the production of anti-adipogenic PGs is critical for the regulation of the early phase of adipogenesis.</description><subject>1-Methyl-3-isobutylxanthine - pharmacology</subject><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Adipogenesis - genetics</subject><subject>Animals</subject><subject>Bucladesine - pharmacology</subject><subject>Cell Differentiation</subject><subject>COX-2</subject><subject>CREB</subject><subject>CREB-Binding Protein - antagonists & inhibitors</subject><subject>CREB-Binding Protein - genetics</subject><subject>CREB-Binding Protein - metabolism</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Dinoprostone - biosynthesis</subject><subject>Gene Expression Regulation</subject><subject>Mice</subject><subject>Okadaic Acid - pharmacology</subject><subject>Phosphoric Diester Hydrolases - genetics</subject><subject>Phosphoric Diester Hydrolases - metabolism</subject><subject>PKA</subject><subject>PP1/2A</subject><subject>Promoter Regions, Genetic</subject><subject>Prostaglandin</subject><subject>Protein Binding</subject><subject>Protein Phosphatase 1 - antagonists & inhibitors</subject><subject>Protein Phosphatase 1 - genetics</subject><subject>Protein Phosphatase 1 - metabolism</subject><subject>Protein Phosphatase 2 - antagonists & inhibitors</subject><subject>Protein Phosphatase 2 - genetics</subject><subject>Protein Phosphatase 2 - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFq3DAQhkVJSTZpHqCX4mMudmcky5LJqVmStBAIlBR6E7I022hZy47kDcnb12bTHHsamPn-H-Zj7DNChYDN123VO6o4oKiQV4D1B7ZCrXipQaojtgIBolQc1Ak7zXkLAEpyfcxOeC2UVkKuGD1Q6kO0Uxhi0ZN7tDHkvhg2xfrn9VXpaaToKU6FdVN4PmDL8f53yQt6GRPlvOxCLMim3WsxPtpMC2J9GIc_FCmH_Il93NhdpvO3ecZ-3Vw_rL-Xd_e3P9bf7kpXYzuVmjpLpLRA13VeerTQeWzAS9IkW3BaAtc1SuKqlb7BBmHTihZqS06KRpyxi0PvmIanPeXJ9CE72u1spGGfDUpolG4brWcUD6hLQ86JNmZMobfp1SCYxa7ZmtmuWewa5Ga2O2e-vNXvu578e-Kfzhm4PAA0P_kcKJnsAkVHPiRyk_FD-E_9X5u1ikc</recordid><startdate>20140325</startdate><enddate>20140325</enddate><creator>Fujimori, Ko</creator><creator>Yano, Mutsumi</creator><creator>Miyake, Haruka</creator><creator>Kimura, Hiroko</creator><general>Elsevier Ireland Ltd</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>7X8</scope><orcidid>https://orcid.org/0000-0002-2506-0769</orcidid></search><sort><creationdate>20140325</creationdate><title>Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis</title><author>Fujimori, Ko ; Yano, Mutsumi ; Miyake, Haruka ; Kimura, Hiroko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-8ebaee7831cbbd5d1a0bd160d5e8e590c85028415e2795d61610f93904aec5363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1-Methyl-3-isobutylxanthine - pharmacology</topic><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Adipogenesis - genetics</topic><topic>Animals</topic><topic>Bucladesine - pharmacology</topic><topic>Cell Differentiation</topic><topic>COX-2</topic><topic>CREB</topic><topic>CREB-Binding Protein - antagonists & inhibitors</topic><topic>CREB-Binding Protein - genetics</topic><topic>CREB-Binding Protein - metabolism</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Dinoprostone - biosynthesis</topic><topic>Gene Expression Regulation</topic><topic>Mice</topic><topic>Okadaic Acid - pharmacology</topic><topic>Phosphoric Diester Hydrolases - genetics</topic><topic>Phosphoric Diester Hydrolases - metabolism</topic><topic>PKA</topic><topic>PP1/2A</topic><topic>Promoter Regions, Genetic</topic><topic>Prostaglandin</topic><topic>Protein Binding</topic><topic>Protein Phosphatase 1 - antagonists & inhibitors</topic><topic>Protein Phosphatase 1 - genetics</topic><topic>Protein Phosphatase 1 - metabolism</topic><topic>Protein Phosphatase 2 - antagonists & inhibitors</topic><topic>Protein Phosphatase 2 - genetics</topic><topic>Protein Phosphatase 2 - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujimori, Ko</creatorcontrib><creatorcontrib>Yano, Mutsumi</creatorcontrib><creatorcontrib>Miyake, Haruka</creatorcontrib><creatorcontrib>Kimura, Hiroko</creatorcontrib><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>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujimori, Ko</au><au>Yano, Mutsumi</au><au>Miyake, Haruka</au><au>Kimura, Hiroko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2014-03-25</date><risdate>2014</risdate><volume>384</volume><issue>1-2</issue><spage>12</spage><epage>22</epage><pages>12-22</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>•IBMX elevated the activity of PKA.•dbcAMP enhanced the phosphorylation of CREB through activation of PKA.•CREB siRNA suppressed the expression of the COX-2.•Okadaic acid repressed the adipogenesis by elevating CREB-dependent COX-2 expression.
We elucidated the molecular mechanism of prostaglandin (PG) E2- and PGF2α-mediated suppression of the early phase of adipogenesis through enhanced COX-2 expression in 3T3-L1 cells. 3-Isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase which catalyzes the conversion of cAMP to AMP, enhanced the activity of protein kinase A (PKA). Dibutyryl cAMP activated PKA and enhanced the phosphorylation of cAMP response element (CRE)-binding protein (CREB). The ability of CREB binding to the CRE of the COX-2 promoter was elevated for enhancement of the expression of the COX-2 gene. CREB siRNA suppressed the expression of the COX-2 gene. Furthermore, okadaic acid, a protein phosphatase (PP) 1/2A inhibitor, suppressed the progression of adipogenesis by preventing PP1/2A-mediated suppression of CREB-dependent COX-2 expression, thus resulting in increased production of anti-adipogenic PGE2 and PGF2α. These results indicate that CREB-dependent expression of COX-2 for the production of anti-adipogenic PGs is critical for the regulation of the early phase of adipogenesis.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>24378735</pmid><doi>10.1016/j.mce.2013.12.014</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2506-0769</orcidid></addata></record> |
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| ispartof | Molecular and cellular endocrinology, 2014-03, Vol.384 (1-2), p.12-22 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 1-Methyl-3-isobutylxanthine - pharmacology 3T3-L1 Cells Adipocytes Adipocytes - cytology Adipocytes - drug effects Adipocytes - metabolism Adipogenesis - genetics Animals Bucladesine - pharmacology Cell Differentiation COX-2 CREB CREB-Binding Protein - antagonists & inhibitors CREB-Binding Protein - genetics CREB-Binding Protein - metabolism Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism Dinoprostone - biosynthesis Gene Expression Regulation Mice Okadaic Acid - pharmacology Phosphoric Diester Hydrolases - genetics Phosphoric Diester Hydrolases - metabolism PKA PP1/2A Promoter Regions, Genetic Prostaglandin Protein Binding Protein Phosphatase 1 - antagonists & inhibitors Protein Phosphatase 1 - genetics Protein Phosphatase 1 - metabolism Protein Phosphatase 2 - antagonists & inhibitors Protein Phosphatase 2 - genetics Protein Phosphatase 2 - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction |
| title | Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis |
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