Navegando por Palavras-chave "Kinases"

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    17 beta-estradiol induces the translocation of the estrogen receptors ESR1 and ESR2 to the cell membrane, MAPK3/1 phosphorylation and proliferation of cultured immature rat Sertoli cells
    (Soc Study Reproduction, 2008-01-01) Lucas, Thais Fabiana Gameiro [UNIFESP]; Siu, Erica Rosanna [UNIFESP]; Esteves, Carlos A. [UNIFESP]; Monteiro, Hugo Pequeno [UNIFESP]; Oliveira, Cleida Aparecida de; Porto, Catarina Segreti [UNIFESP]; Lazari, Maria de Fatima Magalhaes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Minas Gerais (UFMG)
    The aim of the present study was to determine the mechanisms involved in estrogen actions in cultured rat Sertoli cells. RT-PCR detected transcripts for the estrogen receptors ESR1 and ESR2 in cultured immature Sertoli cells and in the testis of 15-, 28-, and 120-day-old rats. the expression of ESR1 and ESR2 was confirmed in Sertoli cells by immunofluorescence and Western blot. Immunohistochemistry with cryosections of testes from immature and adult rats revealed that ESR1 is present in Sertoli, Leydig, and some peritubular myoid cells, and ESR2 is present in multiple cell types, including germ cells. Treatment of Sertoli cells with 17beta-estradiol (E-2) induced a translocation of ESR1 and ESR2 to the plasma membrane and a, concomitant phosphorylation of MAPK3/1. Both effects reached a maximum after 10 min and were blocked by PP2, an inhibitor of the SRC family of protein tyrosine kinases, and by the antiestrogen ICI 182,780 (10). MAPK3/1 phosphorylation was also decreased in the presence of AG 1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase, and in the presence of MAP2K1/2 inhibitor UO126. Treatment with 2 for 24 h increased the incorporation of [methyl-H-3]thymidine, which was blocked by ICI. These results indicate that E2 activates an SRC-mediated translocation of estrogen receptors to the plasma membrane, which results in the activation of EGFR and the mitogen-activated protein kinase signaling pathway. in addition, activation of ESR1 and/or ESR2 by E 2 is involved in proliferation of immature Sertoli cells. the estrogen actions in Sertoli cells might be a key step mediating cellular events important for spermatogenesis and fertility.
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    Síntese de análogos da nifuroxazida potencialmente inibidores da via JAK-STAT
    (Universidade Federal de São Paulo, 2019-12-13) Pavani, Thais Fernanda Amorim [UNIFESP]; Rando, Daniela Gonçales Galasse [UNIFESP]; Universidade Federal de São Paulo
    JAK-like proteins are involved in the transmission of information from the extracellular medium to the nucleus by phosphorylating cytoplasmic peptides known as STAT, which dimerize and thereby migrate to the nucleus by modulating gene expression related to cell division, proliferation and differentiation. For this reason, the exacerbated activation of this pathway is directly linked to proliferative processes such as autoimmune diseases, inflammation and neoplasms. In the search for modulating compounds of these pathways, N-acylidrazone nifuroxazide (NFZ) has been reported as a potential inhibitor of the JAK enzyme. Given the above, this study aimed to explore a series of N-acylhydrazonic compounds, analogous to NFZ, against different tumor cell lines. Ten NFZ analogs were synthesized, which were biologically evaluated against the culture of leukemia, head and neck, prostate and thyroid cancer cells. Faced with leukemic cells, NFZ and GPQF-63 reduced cell viability in a time and dose dependent manner, as well as increased apoptosis and autophagy processes. Cell viability assays with tumor cells showed that only nitrated analogs (NFZ, GPQF-63 and GPQF-803) had significant antiproliferative activity. Studies of free radical production on prostate and thyroid cancer strains, as well as against normal thyroid cells, demonstrate that production of such reactive species occurred only in the presence of thyroid carcinoma cells. The fact that in the presence of prostate tumor cells no free radical production was observed indicates the presence of another mechanism of action for the active derivatives, other than the one commonly associated with the nitro group reduction of these compounds. Molecular docking studies were performed with the non hydroxylated compounds against JAK2 in active (PDB: 4IVA) and inactive (PDB: 3UGC) conformation and the results indicate preference of these compounds for the allosteric site exposed in the inactive conformation of this enzyme. Future experimental and theoretical studies are still needed to understand the mechanism by which compounds that have been shown to be active are acting.