Navegando por Palavras-chave "Calcium channels"

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    Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum
    (Elsevier Science Inc, 2016) Budu, Alexandre [UNIFESP]; Gomes, Mayrim Machado [UNIFESP]; Melo, Pollyana Maria Saud [UNIFESP]; Maluf, Sarah El Chamy [UNIFESP]; Bagnaresi, Piero [UNIFESP]; Azevedo, Mauro Ferreira de; Carmona, Adriana Karaoglanovic [UNIFESP]; Gazarini, Marcos Leoni [UNIFESP]
    Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca2+-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca2+](cyt)) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca2+-free conditions, the [Ca2+](cyt) rise elicited by CZ treatment was similar to 3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca2+/H+ ionophore ionomycin (ION) and the Na+/H+ ionophore monensin (MON) suggest that the [Ca2+](cyt)-increasing effect of CZ is driven by the removal of Ca2+ from at least one Ca2+-CaM-related (CaMR) protein as well as by the mobilization of Ca2+ from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca2+ elicited by CZ. Finally, the modulation of membrane Ca2+ channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co2+ but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca2+ channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca2+ reservoir in the parasite. (C) 2015 Elsevier Inc. All rights reserved.
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    Functional effects of alcohol withdrawal syndrome on peripheral sympathetic neurotransmission in vas deferens of adult rats
    (Elsevier B.V., 2014-07-11) Bomfim, Guilherme Henrique Souza [UNIFESP]; Verde, Luciana Ferreira [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Jurkiewicz, Neide Hyppolito [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Aims: Alcohol withdrawal syndrome (AWS) is characterized by a set of physiological modifications triggered by abrupt withdrawal and/or decreasing consumption of ethanol (EtOH), which May manifest 16-48 h after ceasing consumption. the relationship between the effects of AWS and central and peripheral sympathetic neurotransmission is unknown. This study investigates the possible mechanisms on the sympathetic system during periods of AWS.Main methods: Male Wistar rats were treated with EtOH (6-10 g/kg/day/v.o. 5 days). Subsequently, 1 h, 24 h, 48 h and 120 h after administration of the last dose of EtOH, the animals were sacrificed, and their vas deferens (VD) were removed to perform the following evaluations: (a) concentration-effect curves of sympathetic agonist; (b) activity of alpha(2)-adrenoreceptor; (c) function of voltage-dependent calcium channels (Cav); and (d) release of endogenous catecholamines measured in real time coupled to HPLC.Key findings: the results showed that the maximum effects of contraction were increased by agonists tested in at 24 h and 48 h EtOH withdrawal. the inhibitory affinity (pIC(50)) of guanfacine was decreased 24 h EtOH withdrawal. the function of Cav was also decreased as pIC50 values dropped 24 h and 48 h EtOH withdrawal. the release of catecholamines increased 48 h after EtOH withdrawal. It is suggested that AWS triggers hyperactivity in peripheral sympathetic neurotransmission.Significance: the mechanisms underlying hyperactivity are possibly explained by a failure of autoregulation from catecholamines released by alpha(2)-adrenoreceptors and/or an increase of Cav function, which may be potential targets to attenuate the symptoms of AWS at the peripheral level. (C) 2014 Published by Elsevier Inc.
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    Lower density of L-type and higher density of P/Q-type of calcium channels in chromaffin cells of hypertensive, compared with normotensive rats
    (Elsevier B.V., 2013-04-15) Pascual, Ricardo de; Miranda-Ferreira, Regiane [UNIFESP]; Galvao, Kleber M. [UNIFESP]; Lameu, Claudina; Ulrich, Henning; Smaili, Soraya Soubhi [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Garcia, Antonio G.; Gandia, Luis; Univ Autonoma Madrid; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Enhanced activity of the sympatho-adrenal axis and augmented circulating catecholamines has been implicated in the development of hypertension. Release of catecholamine from stimulated adrenal medulla chromaffin cells has been shown to be higher and longer in spontaneously hypertensive rats (SHRs), compared with normotensive Wistar rats (NWRs). Whether differences in the functional expression of voltage-dependent calcium channels (VDCCs) of the L-, N-, or P/Q subtypes may contribute to such distinct secretory behaviour, is unknown. We therefore approached here this study in voltage-clamped NWR and SHR chromaffin cells, using 10 mM Ba2+ as charge carrier (I-Ba) and selective blockers of each channel type. We found that compared with NWR cells, SHR chromaffin cells exhibited the following differences: (1) 30% diminution of the I-Ba fraction carried by L channels; (2) a doubling of the I-Ba fraction carried by P/Q channels; (3) more visible current modulation by ATP that could be linked to a 10-fold higher mRNA levels for purinergic receptors of the P-2Y2 subtype; and (3) a higher contribution of PQ channels to the transients of the cytosolic calcium concentrations ([Ca2+](c)) generated by K+, compared with L channels. These results may contribute to the better understanding of the greater calcium signalling and exocytotic responses of SHR compared with NWR chromaffin cells, found in three previous reports from our laboratories. (C) 2013 Elsevier B.V. All rights reserved.
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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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    Peptide gomesin triggers cell death through L-type channel calcium influx, MAPK/ERK, PKC and PI3K signaling and generation of reactive oxygen species
    (Elsevier B.V., 2010-07-30) Soletti, Rossana C.; del Barrio, Laura; Daffre, Sirlei; Miranda, Antonio [UNIFESP]; Borges, Helena L.; Moura-Neto, Vivaldo; Lopez, Manuela G.; Gabilan, Nelson H.; Univ Autonoma Madrid; Universidade Federal de Santa Catarina (UFSC); Universidade Federal do Rio de Janeiro (UFRJ); Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Gomesin is an antimicrobial peptide isolated from hemocytes of a common Brazilian tarantula spider named Acanthoscurriagomesiana. This peptide exerts antitumor activity in vitro and in vivo by an unknown mechanism. in this study, the cytotoxic mechanism of gomesin in human neuroblastoma SH-SY5Y and rat pheochromocytoma PC12 cells was investigated. Gomesin induced necrotic cell death and was cytotoxic to SH-SY5Y and PC12 cells. the peptide evoked a rapid and transient elevation of intracellular calcium levels in Fluo-4-AM loaded PC12 cells, which was inhibited by nimodipine, an L-type calcium channel blocker. Preincubation with nimodipine also inhibited cell death induced by gomesin in SH-SY5Y and PC12 cells. Gomesin-induced cell death was prevented by the pretreatment with MAPK/ERK, PKC or PI3K inhibitors, but not with PKA inhibitor. in addition, gomesin generated reactive oxygen species (ROS) in SH-SY5Y cells, which were blocked with nimodipine and MAPK/ERK, PKC or PI3K inhibitors. Taken together, these results suggest that gomesin could be a useful anticancer agent, which mechanism of cytotoxicity implicates calcium entry through L-type calcium channels, activation of MAPK/ERK, PKC and PI3K signaling as well as the generation of reactive oxygen species. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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    Regulação dos canais de cálcio voltagem-dependentes pelo tratamento crônico com nifedipina no ducto deferente de rato e no fundus de estômago
    (Universidade Federal de São Paulo (UNIFESP), 2000) Verde, Luciana Ferreira [UNIFESP]; Jurkiewicz, Neide Hyppolito [UNIFESP]
    Nosso objetivo foi estudar os efeitos decorrentes do tratamento cronico com um antagonista dos canais de calcio voltagem-dependentes do tipo L, no caso a nifedipina, sobre a expressao e a funcao destes canais apos a suspensao do tratamento. Para isto utilizamos dois tipos de musculatura lisa: o ducto deferente e o fundus de estomago provenientes de ratos tratados com nifedipina durante o periodo de vida infantil (do 7§ ao 28§ dia de vida pos-natal) e adulto (por 5 ou 15 dias). Os experimentos foram realizados em animais com 40, 60 e 120 dias de idade tratados durante o periodo infantil, ou seja, 10, 30 e 60 dias apos a suspensao da medicacao, ou entre o 10 e 60 dia de suspensao, quando o tratamento foi feito em animais adultos. A expressao dos VDCCs foi avaliada atraves da ligacao da 3H-isradipina, antagonista dos canais, pela metodologia de receptor-binding enquanto a funcao dos canais foi estudada atraves de experimentos funcionais usando agonistas que contraem a musculatura por mecanismos diferentes. Os principais resultados obtidos foram: 1. O tratamento com nifedipina durante o periodo de vida infantil (entre o 7§ e 28§ dia de vida) produziu, nos DDRS, um aumento da densidade de VDCCs do tipo L, de 34 e 40 por cento, medidos respectivamente 10 e 30 dias apos a suspensao do tratamento. Nos DDRs 90 dias apos a cessacao do tratamento, (animais com 120 dias de idade), este aumento nao foi mais visualizado. 2. Nos DDRS, 10 e 30 dias apos a suspensao do tratamento dos ratos infantis com nifedipina, houve aumento de resposta aos agonistas BaCl2, KCl (animais com 40 e 60 dias) e MeCh (so animais com 60 dias). A isradipina bloqueou completamente estas respostas sugerindo uma relacao direta entre o aumento na densidade dos canais e nas resposta contrateis. 3. A resposta da NOR no DDR nao foi modificada pelo tratamento com nifedipina apesar de ter sido abolida pela isradipina. A existencia de alguma alteracao compensatoria pode estar envolvida. 4. Um aumento na atividade simpatica, por aumento da concentracao de noradrenalina liberada ou no processo de liberacao, fica excluido uma vez que o tratamento de ratos infantis com nifedipina nao alterou a resposta do agonista de acao indireta, tiramina. 5. No fundus de estomago, cerca de 20 a 40 por cento da resposta contratil ao BaCl2 e ao KCI independe da entrada de Ca++ pelos VDCCs do tipo L porque nao e abolida pela isradipina. Entretanto, da mesma forma que ocorreu no DDR, verificou-se um ...(au)