Hematopoietic stem cell expansion caused by a synthetic fragment of leptin
•Leptin is an important cytokine that regulates hematopoiesis.•Six leptin fragments have been synthesized.•LEP5 fragment increases hematopoietic stem cells and colony-forming units.•LEP5 is a positive modulator of hematopoiesis. Leptin is a cytokine that regulates food intake, energy expenditure and...
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creator | Dias, Carol C. Nogueira-Pedro, Amanda Barbosa, Christiano M.V. Ribeiro-Filho, Antonio C. Wasinski, Frederick Araújo, Ronaldo C. de Oliveira Jr, Vani Xavier Miranda, Antonio Paredes-Gamero, Edgar J. |
description | •Leptin is an important cytokine that regulates hematopoiesis.•Six leptin fragments have been synthesized.•LEP5 fragment increases hematopoietic stem cells and colony-forming units.•LEP5 is a positive modulator of hematopoiesis.
Leptin is a cytokine that regulates food intake, energy expenditure and hematopoiesis. Based on the tridimensional structure of the human leptin molecule, six fragments have been synthesized, (Ac-Lep23–47-NH2, [LEP1]; Ac-Lep48–71-NH2, [LEP2]; Ac-Lep72–88-NH2, [LEP3]; Ac-Lep92–115-NH2, [LEP4], Ac-[Ser117]-Lep116–140-NH2, [LEP5] and Ac-Lep141–164-NH2, [LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days. The mature and primitive hematopoietic populations were quantified. We observed that the mature populations from the bone marrow and spleen were not affected by LEP5. However, the peptide caused at least a two-fold increase in the number of hematopoietic stem cells, the most primitive population of the bone marrow. Additionally, the number of granulocyte/macrophage colony-forming units produced by bone marrow cells in methylcellulose also increased by 40% after treatment with LEP5, and the leptin receptor was activated. These results show that the leptin fragment LEP5 is a positive modulator of the in vivo expansion of hematopoietic stem cells. |
doi_str_mv | 10.1016/j.peptides.2013.09.012 |
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Leptin is a cytokine that regulates food intake, energy expenditure and hematopoiesis. Based on the tridimensional structure of the human leptin molecule, six fragments have been synthesized, (Ac-Lep23–47-NH2, [LEP1]; Ac-Lep48–71-NH2, [LEP2]; Ac-Lep72–88-NH2, [LEP3]; Ac-Lep92–115-NH2, [LEP4], Ac-[Ser117]-Lep116–140-NH2, [LEP5] and Ac-Lep141–164-NH2, [LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days. The mature and primitive hematopoietic populations were quantified. We observed that the mature populations from the bone marrow and spleen were not affected by LEP5. However, the peptide caused at least a two-fold increase in the number of hematopoietic stem cells, the most primitive population of the bone marrow. Additionally, the number of granulocyte/macrophage colony-forming units produced by bone marrow cells in methylcellulose also increased by 40% after treatment with LEP5, and the leptin receptor was activated. These results show that the leptin fragment LEP5 is a positive modulator of the in vivo expansion of hematopoietic stem cells.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2013.09.012</identifier><identifier>PMID: 24090593</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; bone marrow ; Bone Marrow Cells - cytology ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - metabolism ; Cell Proliferation - drug effects ; cytokines ; energy expenditure ; food intake ; Gene Expression - drug effects ; hematopoiesis ; Hematopoiesis - drug effects ; hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - drug effects ; Hematopoietic Stem Cells - metabolism ; humans ; Injections, Intraperitoneal ; leptin ; Leptin - pharmacology ; leptin receptors ; macrophages ; Male ; methylcellulose ; Mice ; Mice, Inbred C57BL ; Peptide Fragments - chemical synthesis ; Peptide Fragments - pharmacology ; population ; Receptors, Leptin - agonists ; Receptors, Leptin - genetics ; Receptors, Leptin - metabolism ; spleen ; Spleen - cytology ; Spleen - drug effects ; Spleen - metabolism</subject><ispartof>Peptides (New York, N.Y. : 1980), 2013-12, Vol.50, p.24-27</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-606e6b484281631884648f8baa76d3dcb21ec119aa00db2743e4da1003686b8b3</citedby><cites>FETCH-LOGICAL-c392t-606e6b484281631884648f8baa76d3dcb21ec119aa00db2743e4da1003686b8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.peptides.2013.09.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24090593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dias, Carol C.</creatorcontrib><creatorcontrib>Nogueira-Pedro, Amanda</creatorcontrib><creatorcontrib>Barbosa, Christiano M.V.</creatorcontrib><creatorcontrib>Ribeiro-Filho, Antonio C.</creatorcontrib><creatorcontrib>Wasinski, Frederick</creatorcontrib><creatorcontrib>Araújo, Ronaldo C.</creatorcontrib><creatorcontrib>de Oliveira Jr, Vani Xavier</creatorcontrib><creatorcontrib>Miranda, Antonio</creatorcontrib><creatorcontrib>Paredes-Gamero, Edgar J.</creatorcontrib><title>Hematopoietic stem cell expansion caused by a synthetic fragment of leptin</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>•Leptin is an important cytokine that regulates hematopoiesis.•Six leptin fragments have been synthesized.•LEP5 fragment increases hematopoietic stem cells and colony-forming units.•LEP5 is a positive modulator of hematopoiesis.
Leptin is a cytokine that regulates food intake, energy expenditure and hematopoiesis. Based on the tridimensional structure of the human leptin molecule, six fragments have been synthesized, (Ac-Lep23–47-NH2, [LEP1]; Ac-Lep48–71-NH2, [LEP2]; Ac-Lep72–88-NH2, [LEP3]; Ac-Lep92–115-NH2, [LEP4], Ac-[Ser117]-Lep116–140-NH2, [LEP5] and Ac-Lep141–164-NH2, [LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days. The mature and primitive hematopoietic populations were quantified. We observed that the mature populations from the bone marrow and spleen were not affected by LEP5. However, the peptide caused at least a two-fold increase in the number of hematopoietic stem cells, the most primitive population of the bone marrow. Additionally, the number of granulocyte/macrophage colony-forming units produced by bone marrow cells in methylcellulose also increased by 40% after treatment with LEP5, and the leptin receptor was activated. These results show that the leptin fragment LEP5 is a positive modulator of the in vivo expansion of hematopoietic stem cells.</description><subject>Animals</subject><subject>bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>cytokines</subject><subject>energy expenditure</subject><subject>food intake</subject><subject>Gene Expression - drug effects</subject><subject>hematopoiesis</subject><subject>Hematopoiesis - drug effects</subject><subject>hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>humans</subject><subject>Injections, Intraperitoneal</subject><subject>leptin</subject><subject>Leptin - pharmacology</subject><subject>leptin receptors</subject><subject>macrophages</subject><subject>Male</subject><subject>methylcellulose</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Peptide Fragments - chemical synthesis</subject><subject>Peptide Fragments - pharmacology</subject><subject>population</subject><subject>Receptors, Leptin - agonists</subject><subject>Receptors, Leptin - genetics</subject><subject>Receptors, Leptin - metabolism</subject><subject>spleen</subject><subject>Spleen - cytology</subject><subject>Spleen - drug effects</subject><subject>Spleen - metabolism</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv1DAQhS0EotvCXyg-ckmYiV2vfQNVQEGVOEDPlmNPilebONhe1P33JGzLldNcvvfm6WPsEqFFQPVu18401xiotB2gaMG0gN0ztkG9Fc0VKvOcbQCNasxW4xk7L2UHAFIa_ZKddRIMXBmxYV9vaHQ1zSlSjZ6XSiP3tN9zepjdVGKauHeHQoH3R-54OU71519yyO5-pKnyNPD9OmV6xV4Mbl_o9eO9YHefPv64vmluv33-cv3htvHCdLVRoEj1UstOoxKotVRSD7p3bquCCL7vkDyicQ4g9N1WCpLBIYBQWvW6Fxfs7al3zunXgUq1YyzrZjdROhSLa6GRKLsFVSfU51RKpsHOOY4uHy2CXT3anX3yaFePFoxdPC7By8cfh36k8C_2JG4B3pyAwSXr7nMs9u770qAWyaCF0Qvx_kTQ4uJ3pGyLjzR5CjGTrzak-L8VfwAyaZBL</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Dias, Carol C.</creator><creator>Nogueira-Pedro, Amanda</creator><creator>Barbosa, Christiano M.V.</creator><creator>Ribeiro-Filho, Antonio C.</creator><creator>Wasinski, Frederick</creator><creator>Araújo, Ronaldo C.</creator><creator>de Oliveira Jr, Vani Xavier</creator><creator>Miranda, Antonio</creator><creator>Paredes-Gamero, Edgar J.</creator><general>Elsevier Inc</general><scope>FBQ</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>20131201</creationdate><title>Hematopoietic stem cell expansion caused by a synthetic fragment of leptin</title><author>Dias, Carol C. ; Nogueira-Pedro, Amanda ; Barbosa, Christiano M.V. ; Ribeiro-Filho, Antonio C. ; Wasinski, Frederick ; Araújo, Ronaldo C. ; de Oliveira Jr, Vani Xavier ; Miranda, Antonio ; Paredes-Gamero, Edgar J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-606e6b484281631884648f8baa76d3dcb21ec119aa00db2743e4da1003686b8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>bone marrow</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>cytokines</topic><topic>energy expenditure</topic><topic>food intake</topic><topic>Gene Expression - drug effects</topic><topic>hematopoiesis</topic><topic>Hematopoiesis - drug effects</topic><topic>hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>humans</topic><topic>Injections, Intraperitoneal</topic><topic>leptin</topic><topic>Leptin - pharmacology</topic><topic>leptin receptors</topic><topic>macrophages</topic><topic>Male</topic><topic>methylcellulose</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Peptide Fragments - chemical synthesis</topic><topic>Peptide Fragments - pharmacology</topic><topic>population</topic><topic>Receptors, Leptin - agonists</topic><topic>Receptors, Leptin - genetics</topic><topic>Receptors, Leptin - metabolism</topic><topic>spleen</topic><topic>Spleen - cytology</topic><topic>Spleen - drug effects</topic><topic>Spleen - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dias, Carol C.</creatorcontrib><creatorcontrib>Nogueira-Pedro, Amanda</creatorcontrib><creatorcontrib>Barbosa, Christiano M.V.</creatorcontrib><creatorcontrib>Ribeiro-Filho, Antonio C.</creatorcontrib><creatorcontrib>Wasinski, Frederick</creatorcontrib><creatorcontrib>Araújo, Ronaldo C.</creatorcontrib><creatorcontrib>de Oliveira Jr, Vani Xavier</creatorcontrib><creatorcontrib>Miranda, Antonio</creatorcontrib><creatorcontrib>Paredes-Gamero, Edgar J.</creatorcontrib><collection>AGRIS</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>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dias, Carol C.</au><au>Nogueira-Pedro, Amanda</au><au>Barbosa, Christiano M.V.</au><au>Ribeiro-Filho, Antonio C.</au><au>Wasinski, Frederick</au><au>Araújo, Ronaldo C.</au><au>de Oliveira Jr, Vani Xavier</au><au>Miranda, Antonio</au><au>Paredes-Gamero, Edgar J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematopoietic stem cell expansion caused by a synthetic fragment of leptin</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2013-12-01</date><risdate>2013</risdate><volume>50</volume><spage>24</spage><epage>27</epage><pages>24-27</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract>•Leptin is an important cytokine that regulates hematopoiesis.•Six leptin fragments have been synthesized.•LEP5 fragment increases hematopoietic stem cells and colony-forming units.•LEP5 is a positive modulator of hematopoiesis.
Leptin is a cytokine that regulates food intake, energy expenditure and hematopoiesis. Based on the tridimensional structure of the human leptin molecule, six fragments have been synthesized, (Ac-Lep23–47-NH2, [LEP1]; Ac-Lep48–71-NH2, [LEP2]; Ac-Lep72–88-NH2, [LEP3]; Ac-Lep92–115-NH2, [LEP4], Ac-[Ser117]-Lep116–140-NH2, [LEP5] and Ac-Lep141–164-NH2, [LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days. The mature and primitive hematopoietic populations were quantified. We observed that the mature populations from the bone marrow and spleen were not affected by LEP5. However, the peptide caused at least a two-fold increase in the number of hematopoietic stem cells, the most primitive population of the bone marrow. Additionally, the number of granulocyte/macrophage colony-forming units produced by bone marrow cells in methylcellulose also increased by 40% after treatment with LEP5, and the leptin receptor was activated. These results show that the leptin fragment LEP5 is a positive modulator of the in vivo expansion of hematopoietic stem cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24090593</pmid><doi>10.1016/j.peptides.2013.09.012</doi><tpages>4</tpages></addata></record> |
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subjects | Animals bone marrow Bone Marrow Cells - cytology Bone Marrow Cells - drug effects Bone Marrow Cells - metabolism Cell Proliferation - drug effects cytokines energy expenditure food intake Gene Expression - drug effects hematopoiesis Hematopoiesis - drug effects hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism humans Injections, Intraperitoneal leptin Leptin - pharmacology leptin receptors macrophages Male methylcellulose Mice Mice, Inbred C57BL Peptide Fragments - chemical synthesis Peptide Fragments - pharmacology population Receptors, Leptin - agonists Receptors, Leptin - genetics Receptors, Leptin - metabolism spleen Spleen - cytology Spleen - drug effects Spleen - metabolism |
title | Hematopoietic stem cell expansion caused by a synthetic fragment of leptin |
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