Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP 04044-020, Brazil.
Peptides. 2013 Dec;50:24-7. doi: 10.1016/j.peptides.2013.09.012. Epub 2013 Oct 1.
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-[Ser(117)]-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.
瘦素是一种细胞因子，可调节食物摄入、能量消耗和造血。基于人瘦素分子的三维结构，已合成了六个片段，（Ac-Lep23-47-NH2，[LEP1]；Ac-Lep48-71-NH2，[LEP2]；Ac-Lep72-88-NH2，[LEP3]；Ac-Lep92-115-NH2，[LEP4]，Ac-[Ser(117)]-Lep116-140-NH2，[LEP5]和 Ac-Lep141-164-NH2，[LEP6]），并评估了它们对造血的影响。用 1mg/kg LEP5 处理小鼠 3 天。量化成熟和原始造血群体。我们观察到，LEP5 对骨髓和脾脏中的成熟群体没有影响。然而，该肽至少使骨髓中最原始的造血干细胞数量增加了两倍。此外，在用 LEP5 处理后，骨髓细胞在甲基纤维素中产生的粒细胞/巨噬细胞集落形成单位的数量也增加了 40%，并且瘦素受体被激活。这些结果表明，瘦素片段 LEP5 是体内造血干细胞扩增的正调节剂。
