Hematopoietic stem cell expansion caused by a synthetic fragment of leptin

Author(s)

Dias, Carol C. ^[1] ; Nogueira-Pedro, Amanda ^[2] ; Barbosa, Christiano M. V. ^[2] ; Ribeiro-Filho, Antonio C. ^[1] ; Wasinski, Frederick ^[2] ; Araujo, Ronaldo C. ^[2] ; de Oliveira, Jr., Vani Xavier ^[3] ; Miranda, Antonio ^[2] ; Paredes-Gamero, Edgar J. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo - Brazil

^[3] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP - Brazil

• Document type: Journal article
• Source: Peptides; v. 50, p. 24-27, DEC 2013.
• Web of Science Citations: 8

Abstract

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-Lep(23-47)-NH2, {[}LEP1]; Ac-Lep(48-71)-NH2, {[}LEP2]; Ac-Lep(72-88)-NH2, {[}LEP3]; Ac-Lep(92-115)-NH2, {[}LEP4], Ac-{[}Ser(117)]-Lep(116-140)-NH2, {[}LEP5] and Ac-Lep(141-164)-NH2, {[}LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1 mg/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. (C) 2013 Elsevier Inc. All rights reserved. (AU)