Investigating the role of intracellular Ca2+ as a modulator of leukemic and hematopoietic stem cells

• Grant number: 15/16799-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: January 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Edgar Julian Paredes-Gamero
• Grantee: Edgar Julian Paredes-Gamero
• Host Institution: Pró-Reitoria Acadêmica. Universidade de Mogi das Cruzes (UMC). Campus da Sede Mogi das Cruzes. Mogi das Cruzes , SP, Brazil
• Associated researchers: Alice Teixeira Ferreira

Abstract

The intracellular Ca2+ is the most versatile second messenger. This ion participates in several cellular processes such as proliferation, differentiation, cell death, contraction, secretion, and even at fertilization and learning. These cellular processes are regulated by temporal, spatial and intensity variation of this ion. Our group has been studying the role of Ca2+ ion in the proliferation and differentiation of hematopoietic stem cell. So far we have determined that small increases of intracellular Ca2+ caused by cytokines are related to proliferation of HSC without decreasing their amount. On the other hand large increases of the intracellular Ca2+, caused by purinergic agonists, lead to differentiation of HSC. This effect has been observed in both murine and human HSC. However, a detailed description of Ca2+ ions events that modulate the proliferation and differentiation of HSC in their progeny, details such as location, signal strength and frequency is still needed. In addition, the Ca2+ signaling that leads to proliferation or differentiation is related with proteins which regulate hematopoiesis, and are sensitive to variations of calcium ion, however these proteins that have not yet been identified. Thus, in this project we want to better explore the intracellular Ca2+ signaling pathway by investigating important aspects of Ca2+ signaling such as spatial, temporal and intensity features and try to correlate them to the activation of signaling proteins that regulate hematopoiesis. Then, once identified the pattern of Ca2+ signaling in normal HSC, we want to compare this signal with the leukemic stem cells extracted from a murine leukemic lineage. (AU)

Scientific publications

(4)

(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)

DE REZENDE, MARINA MASTELARO; NG-BLICHFELDT, JOHN-POUL; JUSTO, GISELLE ZENKER; PAREDES-GAMERO, EDGAR JULIAN; GOSENS, REINOUD. Divergent effects of Wnt5b on IL-3-and GM-CSF-induced myeloid differentiation. CELLULAR SIGNALLING, v. 67, MAR 2020. (15/16799-3, 15/24464-1, 16/23787-4)

VITEK, RENAN; DE NOVAIS, LEICE M. R.; TORQUATO, HERON F. V.; PAREDES-GAMERO, EDGAR J.; DE CARVALHO, MARIO G.; DE SOUSA, JR., PAULO T.; JACINTO, MARCOS J.; DA SILVA, VIRGINIA C.. Chemical constituents and antileukemic activity of Eugenia dysenterica. NATURAL PRODUCT RESEARCH, v. 31, n. 16, p. 1930-1934, 2017. (15/16799-3)

RIBEIRO-FILHO, ANTONIO CARLOS; BURI, MARCUS VINICIUS; BARROS, CARLOS CASTILHO; DREYFUSS, JULIANA LUPORINI; NADER, HELENA BONCIANI; JUSTO, GISELLE ZENKER; CRAVEIRO, ROGERIO BASTOS; PESQUERO, JOAO BOSCO; MIRANDA, ANTONIO; FERREIRA, ALICE TEIXEIRA; et al. Functional and molecular evidence for heteromeric association of P2Y(1) receptor with P2Y(2) and P2Y(4) receptors in mouse granulocytes. BMC PHARMACOLOGY & TOXICOLOGY, v. 17, JUL 7 2016. (15/16799-3, 13/09068-7)

VIEIRA TORQUATO, HERON F.; RIBEIRO-FILHO, ANTONIO C.; BURI, MARCUS V.; ARAUJO JUNIOR, ROBERTO T.; PIMENTA, RENATA; DE OLIVEIRA, JOSE SALVADOR R.; FILHO, VALDIR C.; MACHO, ANTONIO; PAREDES-GAMERO, EDGAR J.; DE OLIVEIRA MARTINS, DOMINGOS T.. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 4, p. 958-967, APR 2017. (15/16799-3)