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Molecular mechanisms studies in differentiation and cell death by antimicrobial peptides using leukemic and adenocarcinoma cells

Grant number: 12/20989-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2014
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Edgar Julian Paredes-Gamero
Grantee:Marcus Vinicius Buri
Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):15/22901-5 - Photothermal heterodyne image Microscopy single molecule tracking of antimicrobial peptide, BE.EP.DR


The antimicrobial peptides (AMPs) are defense molecules found in different organisms. But, besides its antimicrobial activity, different papers have shown other potentials of these peptides, among then, the antitumoral ability. Our group showed the cytotoxic activity of some PAMs with b-haipin structure (protegrin, tachyplesin, polyphemusin and gomesin) and the action mechanisms that led to the cell death in myeloid eritroleukemic lineages and other kinds of cell as melanoma, neuroblastoma and Chinese hamster ovary cell. We described that those AMPs cause direct membrane destructuring with high concentrations, but different cell events and death with lower doses, varying the AMPs used, although they share great homology between their aminoacid sequence and structure. The present work aims continuing the studies of the AMPs (protegrin, tachyplesin, polyphemusin and gomesin) antileukemic activity, been made: 1) Citotoxic effects comparison between normal and leukemics cells (HL-60, K562 e KG-1), evaluating the molecular and biochemical death events. 2) Differentiation capacity evaluation from AMPs in leukemic stem cells found in leukemic lineages (HL-60, K562 e KG-1). 3) Furthermore, based in our previous studies, in which we have seen morphological differences in cell, we intend to connect this change in cell with the cellular death effects, using advanced computational image techniques and multiparametric analysis, by flow cytometry and fluorescence conventional and confocal microscopy in HELA adhenocarcinoma cells. All the links between the obtained data will be made using computational/mathematic tools.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BURI, MARCUS VINICIUS; SPERANDIO, LETICIA PAULINO; DE SOUZA, KAMYLLA F. S.; ANTUNES, FERNANDA; REZENDE, MARINA MASTELARO; MELO, CARINA MUCCIOLO; PINHAL, MARIA A. S.; BARROS, CARLOS C.; FERNIG, DAVID G.; YATES, EDWIN A.; et al. Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by beta-Hairpin Antimicrobial Peptides. ACS APPLIED BIO MATERIALS, v. 4, n. 8, p. 6488-6501, . (13/09068-7, 15/22901-5, 12/20989-4)
BURI, MARCUS V.; DIAS, CAROL C.; BARBOSA, CHRISTIANO M. V.; NOGUEIRA-PEDRO, AMANDA; RIBEIRO-FILHO, ANTONIO C.; MIRANDA, ANTONIO; PAREDES-GAMERO, EDGAR J.. Gomesin acts in the immune system and promotes myeloid differentiation and monocyte/macrophage activation in mouse. Peptides, v. 85, p. 41-45, . (13/09068-7, 15/22901-5, 11/17584-0, 12/20989-4)
BURI, MARCUS V.; VIEIRA TORQUATO, HERON F.; BARROS, CARLOS CASTILHO; IDE, JAIME S.; MIRANDA, ANTONIO; PAREDES-GAMERO, EDGAR J.. Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of beta-Hairpin Antimicrobial Peptides. Journal of Cellular Biochemistry, v. 118, n. 7, p. 1764-1773, . (11/17584-0, 12/20989-4, 13/09068-7)

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