Navegando por Palavras-chave "Calcium signalling"

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    Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis
    (Churchill Livingstone, 2011-10-01) Maroto, Marcos; Diego, Antonio M. G. de; Albinana, Elisa; Fernandez-Morales, Jose C.; Caricati-Neto, Afonso [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Yanez, Matilde; Isabel Rodriguez-Franco, Maria; Conde, Santiago; Arce, Mariana P.; Hernandez-Guijo, Jesus M.; Garcia, Antonio G.; Univ Autonoma Madrid; CSIC; Universidade Federal de São Paulo (UNIFESP); Univ Santiago de Compostela
    Compound ITH33/IQM9.21 (ITH/IQM) belongs to a new family of L-glutamic acid derivatives with antioxidant and neuroprotective properties on in vitro and in vivo models of stroke. Because neuronal damage after brain ischemia is tightly linked to excess Ca2+ entry and neuronal Ca2+ overload, we have investigated whether compound ITH/IQM antagonises the elevations of the cytosolic Ca2+ concentrations ([Ca2+](c)) and the ensuing exocytotic responses triggered by depolarisation of bovine chromaffin cells. in fluo-4-loaded cell populations, ITH/IQM reduced the K+-evoked [Ca2+](c) transients with an IC50 of 5.31 mu M. At 10 mu M, the compound decreased the amplitude and area of the Ca2+ transient elicited by challenging single fura-2-loaded cells with high K+ by 40% and 80%, respectively. This concentration also caused a blockade of K+-induced catecholamine release at the single-cell level (78%) and cell populations (55%). These effects are likely due to blockade of the whole-cell inward Ca2+ currents (IC50 = 6.52 mu M). At 10 mu M, ITH/IQM also inhibited the Ca2+-dependent outward K+ current, leaving untouched the voltage-dependent component of I-K. the inward Na+ current was unaffected. Inhibition of depolarisation-elicited Ca2+ entry, [Ca2+](c) elevation and exocytosis could contribute to the neuroprotective effects of ITH/IQM in vulnerable neurons undergoing depolarisation during brain ischemia. (C) 2011 Elsevier B.V. All rights reserved.
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    Palladacycle (BPC) antitumour activity against resistant and metastatic cell lines: the relationship with cytosolic calcium mobilisation and cathepsin B activity
    (Elsevier B.V., 2014-05-22) Bechara, Alexandre [UNIFESP]; Barbosa, Christiano Marcello Vaz [UNIFESP]; Paredes-Gamero, Edgar Julian [UNIFESP]; Garcia, Daniel Moreno [UNIFESP]; Silva, Luis S. [UNIFESP]; Matsuo, Alisson Leonardo [UNIFESP]; Nascimento, Fábio Dupart; Rodrigues, Elaine Guadelupe [UNIFESP]; Caires, Antonio Carlos Favero; Smaili, Soraya Soubhi [UNIFESP]; Bincoletto, Claudia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Bandeirante São Paulo UNIBAN; Univ Mogi das Cruzes
    The search for new compounds that induce p53-independent apoptosis is the focus of many studies in cancer biology because these compounds could be more specific and would overcome chemotherapy resistance. in this study, we evaluated the in vitro antitumour activity of a Biphosphinic Palladacycle Complex (BPC) and extended preclinical studies to an in vivo model. Saos-2 cells, a p53-null human osteosarcoma drug-resistant cell line, were treated with BPC in the presence or absence of a cathepsin B inhibitor and a calcium chelator (CA074 and BAPTA-AM, respectively), and several parameters related to apoptosis were evaluated. Preclinical studies were performed with mice that were intravenously inoculated with murine melanoma Bl6F10-Nex2 cells and treated intraperitoneally (i.p.) with BPC (8 mg/kg/ day) for ten consecutive days, when lung metastatic nodules were counted. in vitro data show that BPC induces cell death in Saos-2 cells mainly by apoptosis, which was accompanied by the effector caspase-3 activation. These events are most likely related to Bax translocation and increased cytosolic calcium mobilisation, mainly from intracellular compartments. Lysosomal Membrane Permeabilisation (LMP) was also observed after 12 h of BPC exposure. Interestingly, BAPTA-AM and CA074 significantly decreased BPC cytotoxicity, suggesting that both calcium and cathepsin B are required for BPC antitumour activity. in vivo studies demonstrated that BPC protects mice against murine metastatic melanoma. in conclusion, BPC complex is an effective anticancer compound against metastatic murine melanoma. This complex is cytotoxic to the drug-resistant osteosarcoma Saos-2 human tumour cells by inducing apoptosis triggered by calcium signalling and a lysosomal-dependent pathway. (C) 2014 Elsevier Masson SAS. All rights reserved.