A synthetic fragment of leptin increase hematopoietic stem cell population and improve its engraftment ability.
Several studies have shown the important actions of cytokine leptin that regulates food intake and energy expenditure. Additionally, the ability to modulate hematopoiesis has also been demonstrated. Previous reports have shown that some synthetic sequences of leptin molecules can activate leptin receptor. Herein, decapeptides encompassing amino acids from positions 98 to 122 of the leptin molecule were constructed to evaluate their effects on hematopoiesis. Among them, the synthetic peptide Lep(110-119)-NH2 (LEP F) was the only peptide that possessed the ability to increase the percentage of hematopoietic stem cells (HSC). Moreover, LEP F also produced an increase of granulocyte/macrophage colony-forming units and activated leptin receptor. Furthermore, LEP F also improves the grafting of HSC in bone marrow, but did not accelerate the recovery of bone marrow after ablation with 5-fluorouracil. These results show that LEP F is a positive modulator of the in vivo expansion of HSC and could be useful in bone marrow transplantation.
Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Carolina C
CC
Dias
Departmento de Biofísica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Amanda
A
Nogueira-Pedro
Departmento de Biofísica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Paula Yumi
PY
Tokuyama
Departmento de Biofísica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Marta N C
MN
Martins
Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, R. Napoleão de Barros, 715, São Paulo, Brazil.
Helena Regina Comodo
HR
Segreto
Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Marcus V
MV
Buri
Departmento de Biofísica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
Antonio
A
Miranda
Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.|Centro Interdisciplinar de Investigação Bioquímica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP, Brazil.
Edgar J
EJ
Paredes-Gamero
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D054411:Receptors, Leptin / Q000378:metabolism*
D020738:Leptin; D010446:Peptide Fragments; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; LEPTIN; SYNTHETIC PEPTIDES