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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Veröffentlicht in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2013-12, Vol.50, p.24-27
Hauptverfasser: 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.
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container_issue
container_start_page 24
container_title Peptides (New York, N.Y. : 1980)
container_volume 50
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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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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