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    Avaliação da modulação de células-tronco hematopoéticas por fragmentos sintéticos da leptina
    (Universidade Federal de São Paulo (UNIFESP), 2014-09-24) Dias, Carolina Carvalho [UNIFESP]; Gamero, Edgar Julian Paredes Gamero [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Leptin is a cytokine composed of 167 a i o acids first described as a satiety hormone that regulates body weight and energy expenditure. In the body, leptin has numerous functions in different tissues. In hematopoiesis, previous studies have demonstrated its potential in the differentiation and/or cell proliferation. The group of Dr. Antonio de Miranda, from Department of Biophysics of UNIFESP, has developed human and murine leptin synthetic peptide fragments, whose sequences included portions of the a helical region of the leptin molecule. Two of these human sequence peptides, Ac-hLEP92-11S-NH2and Ac-[Ser117]-hLEP116_140- NH2 have shown activity in a similar manner to the entire protein. Additionally, similar results were obtained with another homologous peptide sequence of mouse, the Ac-mLEP98-122-NH2.This study aimed to evaluate the modulation of hematopoiesis by human and murine synthetic peptides (based on sequences previously tested). The human, Ac-[Ser117]-hLEP116_140-NH2(LEP5), and murine, Ac-mLEP110-119-NH2(LEPF), sequence induced an increase of hematopoietic stem cell (HSC) and clonogenic capacity, as well as, activated Jak2 in HSC. Moreover, the fragment LEPF improved the engraftment of HSC after radiation, however did not accelerate bone marrow regeneration after the chemotherapy with 5-FU. The fragment LEPF only increased HSC after 5-FU treatment. Thus, the bioactive synthetic fragments of leptin could be used to improve the engraftment of HSC is some clinical situation such as HSC transplantation.