Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness
AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular dis...
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| Veröffentlicht in: | Biochemical pharmacology 2005-07, Vol.70 (2), p.308-316 |
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| creator | de Rijke, Corine E. Jackson, Pilgrim J. Garner, Keith M. van Rozen, Rea J. Douglas, Nick R. Kas, Martien J.H. Millhauser, Glenn L. Adan, Roger A.H. |
| description | AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions. |
| doi_str_mv | 10.1016/j.bcp.2005.04.033 |
| format | Article |
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In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2005.04.033</identifier><identifier>PMID: 15927146</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Agouti related protein ; Alanine - genetics ; Animals ; Anorexia ; Anorexia Nervosa - genetics ; Biological and medical sciences ; Cell Line ; Cricetinae ; Dose-Response Relationship, Drug ; Eating - drug effects ; Eating - genetics ; Humans ; Injections, Intraventricular ; Intercellular Signaling Peptides and Proteins ; Medical sciences ; Melanocortin receptor ; Pharmacology. Drug treatments ; Polymorphism ; Polymorphism, Genetic - genetics ; Proteins - administration & dosage ; Proteins - genetics ; Rats ; Rats, Wistar ; Recombinant expression ; Thinness - genetics ; Threonine - genetics ; Weight regulation</subject><ispartof>Biochemical pharmacology, 2005-07, Vol.70 (2), p.308-316</ispartof><rights>2005 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-19bde418b57ecbf6593348634d7d706a3e6f9de59512ce8f0d13a115a7bf87373</citedby><cites>FETCH-LOGICAL-c455t-19bde418b57ecbf6593348634d7d706a3e6f9de59512ce8f0d13a115a7bf87373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006295205002777$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16907515$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15927146$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Rijke, Corine E.</creatorcontrib><creatorcontrib>Jackson, Pilgrim J.</creatorcontrib><creatorcontrib>Garner, Keith M.</creatorcontrib><creatorcontrib>van Rozen, Rea J.</creatorcontrib><creatorcontrib>Douglas, Nick R.</creatorcontrib><creatorcontrib>Kas, Martien J.H.</creatorcontrib><creatorcontrib>Millhauser, Glenn L.</creatorcontrib><creatorcontrib>Adan, Roger A.H.</creatorcontrib><title>Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.</description><subject>Agouti related protein</subject><subject>Alanine - genetics</subject><subject>Animals</subject><subject>Anorexia</subject><subject>Anorexia Nervosa - genetics</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cricetinae</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eating - drug effects</subject><subject>Eating - genetics</subject><subject>Humans</subject><subject>Injections, Intraventricular</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Medical sciences</subject><subject>Melanocortin receptor</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Proteins - administration & dosage</subject><subject>Proteins - genetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Recombinant expression</subject><subject>Thinness - genetics</subject><subject>Threonine - genetics</subject><subject>Weight regulation</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhB3BBvsBtgx3HdiJOVUUpUiUu5Ww59oT1yomDJyndf4-XXak3ehmPn755Gs0j5D1nFWdcfd5XvZurmjFZsaZiQrwgG95qsa071b4kG8aYKr2sL8gbxP3x2yr-mlxw2dWaN2pDHm_WyS0hTTZSW8oBA9I00GUH9Cpape93mc4pHsaU513AkYaJ2l9pXQLNEO0Cns45LXCUEZML_6Q_YdkVv5ThMVg6QX5IaIvgaQQ7TYD4lrwabER4d34vyc-br_fXt9u7H9--X1_dbV0j5bLlXe-h4W0vNbh-ULITommVaLz2mikrQA2dB9lJXjtoB-a5sJxLq_uhXEKLS_Lp5Fu2_L0CLmYM6CBGO0Fa0SjdNVK13bMg10JpJlUB-Ql0OSFmGMycw2jzwXBmjrmYvSm5mGMuhjWm5FJmPpzN134E_zRxDqIAH8-ARWfjkO3kAj5xqmNaclm4LycOys0eAmSDLsDkwIcMbjE-hf-s8RdYr6xg</recordid><startdate>20050715</startdate><enddate>20050715</enddate><creator>de Rijke, Corine E.</creator><creator>Jackson, Pilgrim J.</creator><creator>Garner, Keith M.</creator><creator>van Rozen, Rea J.</creator><creator>Douglas, Nick R.</creator><creator>Kas, Martien J.H.</creator><creator>Millhauser, Glenn L.</creator><creator>Adan, Roger A.H.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20050715</creationdate><title>Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness</title><author>de Rijke, Corine E. ; Jackson, Pilgrim J. ; Garner, Keith M. ; van Rozen, Rea J. ; Douglas, Nick R. ; Kas, Martien J.H. ; Millhauser, Glenn L. ; Adan, Roger A.H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-19bde418b57ecbf6593348634d7d706a3e6f9de59512ce8f0d13a115a7bf87373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Agouti related protein</topic><topic>Alanine - genetics</topic><topic>Animals</topic><topic>Anorexia</topic><topic>Anorexia Nervosa - genetics</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cricetinae</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eating - drug effects</topic><topic>Eating - genetics</topic><topic>Humans</topic><topic>Injections, Intraventricular</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Medical sciences</topic><topic>Melanocortin receptor</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Proteins - administration & dosage</topic><topic>Proteins - genetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Recombinant expression</topic><topic>Thinness - genetics</topic><topic>Threonine - genetics</topic><topic>Weight regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Rijke, Corine E.</creatorcontrib><creatorcontrib>Jackson, Pilgrim J.</creatorcontrib><creatorcontrib>Garner, Keith M.</creatorcontrib><creatorcontrib>van Rozen, Rea J.</creatorcontrib><creatorcontrib>Douglas, Nick R.</creatorcontrib><creatorcontrib>Kas, Martien J.H.</creatorcontrib><creatorcontrib>Millhauser, Glenn L.</creatorcontrib><creatorcontrib>Adan, Roger A.H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Rijke, Corine E.</au><au>Jackson, Pilgrim J.</au><au>Garner, Keith M.</au><au>van Rozen, Rea J.</au><au>Douglas, Nick R.</au><au>Kas, Martien J.H.</au><au>Millhauser, Glenn L.</au><au>Adan, Roger A.H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2005-07-15</date><risdate>2005</risdate><volume>70</volume><issue>2</issue><spage>308</spage><epage>316</epage><pages>308-316</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15927146</pmid><doi>10.1016/j.bcp.2005.04.033</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Agouti related protein Alanine - genetics Animals Anorexia Anorexia Nervosa - genetics Biological and medical sciences Cell Line Cricetinae Dose-Response Relationship, Drug Eating - drug effects Eating - genetics Humans Injections, Intraventricular Intercellular Signaling Peptides and Proteins Medical sciences Melanocortin receptor Pharmacology. Drug treatments Polymorphism Polymorphism, Genetic - genetics Proteins - administration & dosage Proteins - genetics Rats Rats, Wistar Recombinant expression Thinness - genetics Threonine - genetics Weight regulation |
| title | Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness |
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