No description available.

No / Rapid exposure of cardiac muscle to high concentrations of caffeine releases Ca 2+ from the sarcoplasmic reticulum (SR). This Ca 2+ is then extruded from the cell by the Na +/Ca 2+ exchanger. Measurement of the current carried by the exchanger ( I Na/Ca) can therefore be used to estimate of the Ca 2+ content of the SR. Previous studies have shown that caffeine, however, can also inhibit K + currents. We therefore investigated whether the inhibitory effects of caffeine on these currents could contaminate measurements of I Na/Ca. Caffeine caused partial inhibition of the inward rectifier K + current ( I K1): the outward current at ¿40 mV was 1.15±0.24 pA/pF in control and decreased to 0.34±0.15 pA/pF in the presence of 10 mmol/l caffeine ( P<0.05, n=15). This was similar to the effect of caffeine on the holding current observed at ¿40 mV in the absence of K + channel block and could therefore account for the contaminating effects of caffeine observed during measurements of I Na/Ca. Moreover, caffeine also partially inhibited the transient outward ( I to) and the delayed rectifier ( I K) K + currents.

No / Introduction: Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. Materials and methods: We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. Results: Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6 ± 13.5 vs. 296.2 ± 16.2ms; p< 0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91 ± 46 vs. 81 ± 20 nM). Discussion: These data show that the optical AP recorded ratiometrically using di-8- ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than conventional electrophysiological techniques and, when coupled to ventricular myocytes, decreases animal usage and facilitates higher throughput assays.

A creatina (Cr) é uma reserva de fosfato de alta energia, sendo a fonte mais rápida de restauração do ATP intracelular. O hormônios tireoideano participa de forma importante na manutenção da taxa metabólica, aumentando a síntese e consumo de ATP, por meio da regulação de diferentes genes-alvo. Neste sentido, avaliamos o efeitos do HT sobre a expressão gênica do transportador de Cr nos músculos esqueléticos e cardíaco de ratos. O tratamento com o hormônio regula estes processos, porém de forma distinta nos diferentes tipos de músculos. / Creatine (Cr) is a high-energy phosphate reservoir and the fastest source for intracellular ATP regeneration. The thyroid hormone plays a key role on the maintenance of basal metabolic rate, increasing the synthesis and the degradation of ATP through regulation of target-genes. In this study, we explore the effects of thyroid hormone on Cr transporter gene expression and regulation of intracellular pool of Cr in skeletal and cardiac muscles in rats. The hormone can regulate these processes in distinct ways in different muscle types.

A creatina (Cr) é uma reserva de fosfato de alta energia, sendo a fonte mais rápida de restauração do ATP intracelular. O hormônios tireoideano participa de forma importante na manutenção da taxa metabólica, aumentando a síntese e consumo de ATP, por meio da regulação de diferentes genes-alvo. Neste sentido, avaliamos o efeitos do HT sobre a expressão gênica do transportador de Cr nos músculos esqueléticos e cardíaco de ratos. O tratamento com o hormônio regula estes processos, porém de forma distinta nos diferentes tipos de músculos. / Creatine (Cr) is a high-energy phosphate reservoir and the fastest source for intracellular ATP regeneration. The thyroid hormone plays a key role on the maintenance of basal metabolic rate, increasing the synthesis and the degradation of ATP through regulation of target-genes. In this study, we explore the effects of thyroid hormone on Cr transporter gene expression and regulation of intracellular pool of Cr in skeletal and cardiac muscles in rats. The hormone can regulate these processes in distinct ways in different muscle types.

No description available.

No description available.

Dues à leur importance croissante dans la dégénérescence musculaire, les mitochondries sont de plus en plus étudiées en relation à diverses myopathies. Leurs mécanismes de contrôle de qualité sont reconnus pour leur rôle important dans la santé mitochondrial. Dans cette étude, nous tentons de déterminer si le déficit de mitophagie chez les souris déficiente du gène Parkin causera une exacerbation des dysfonctions mitochondriales normalement induite par la doxorubicine. Nous avons analysé l’impact de l’ablation de Parkin en réponse à un traitement à la doxorubicine au niveau du fonctionnement cardiaque, des fonctions mitochondriales et de l’enzymologie mitochondriale. Nos résultats démontrent qu’à l’état basal, l’absence de Parkin n’induit pas de pathologie cardiaque mais est associé à des dysfonctions mitochondriales multiples. La doxorubicine induit des dysfonctions respiratoires, du stress oxydant mitochondrial et une susceptibilité à l’ouverture du pore de transition de perméabilité (PTP). Finalement, contrairement à notre hypothèse, l’absence de Parkin n’accentue pas les dysfonctions mitochondriales induites par la doxorubicine et semble même exercer un effet protecteur. / Mitochondria are becoming the focus of many studies because of their increasingly important role in cellular damage and related myopathies. Their endogenous quality control mechanisms are recognized for their crucial role in mitochondrial health. In our study, we attempted to determine if the deficit of mitophagy in Parkin deficient mice would cause an exacerbation of mitochondrial dysfunctions usually induced by doxorubicin. We have analyzed the impact of the ablation of Parkin in response to treatment with doxorubicin at the level of cardiac functions, mitochondrial functions as well as mitochondrial enzymology. Our results demonstrated that at baseline, the absence of Parkin didn’t induce cardiac pathologies but was associated with many mitochondrial dysfunctions. Doxorubicin induced respiratory dysfunctions, mitochondrial oxidative stress as well as greater susceptibility to permeability transition pore (PTP) opening. Finally, contrary to our hypothesis, the absence of Parkin, didn’t exacerbate mitochondrial dysfunctions induced by doxorubicin and seemed to have a protective effect.

O ferro (Fe) é um oligoelemento capaz de aceitar e doar elétrons. Tal propriedade o torna extremamente útil em diversos componentes importantes ao bom funcionamento do organismo e da célula. O Fe está associado a algumas proteínas, está presente em citocromos, em moléculas que se ligam ao oxigênio (hemoglobina e mioglobina) e em uma grande variedade de enzimas. O aumento e a diminuição da sua oferta levam a alterações na expressão de RNAs mensageiros e proteínas responsáveis pela sua própria homeostase. Sabe-se que a expressão de vários genes envolvidos no metabolismo do Fe é regulada pós-transcricionalmente, por meio de mecanismo que é desencadeado por sua ligação em regiões não traduzíveis presentes em mRNAs específicos, o que interfere no seu grau de poliadenilação, e por conseguinte, na estabilidade e na tradução do transcrito. A Mb é uma heme-proteína de 18,8 kDa, altamente expressa no tecido muscular esquelético e cardíaco, e que pertence a mesma família da hemoglobina. Sabendo-se que cerca de 15% do Fe existente no organismo está presente nos músculos, no presente trabalho avaliamos se a suplementação e restrição de Fe, a curto e longo prazo, alteram a expressão gênica da Mb no músculo oxidativo Soleus (S), glicolítico Extensor Digital Longo (EDL) e no cardíaco. Observamos que a restrição de Fe, a longo prazo, provocou um aumento na expressão gênica e protéica da Mb, apenas no músculo Soleus, sem alterar o grau de poliadenilação do transcrito, enquanto a suplementação não alterou os parâmetros avaliados em nenhum dos tecidos. A administração aguda de Fe não alterou a expressão gênica e protéica da Mb, nem o grau de poliadenilação do transcrito em nenhum dos tecidos estudados. Estes resultados sugerem que a regulação da expressão da Mb pelo Fe se dá apenas transcricionalmente, e de maneira tecido específica. / Iron is a trace element that can accept and donate electrons. This property makes iron extremely important to several components involved with the proper functioning of the organism and cells. Iron is associated with some proteins, is present in cytochromes, molecules that bind to oxygen (hemoglobin and myoglobin) and a variety of enzymes. The increase and decrease of its offer lead to changes in the expression of mRNAs and proteins responsible for their own homeostasis. It is known that the expression of several genes involved in the metabolism of iron is regulated post-transcriptionally through a mechanism that is triggered by its binding in non-translatable regions of specific mRNAs, which interferes with their polyadenylation, and as a consequence, with the stability and translation of the transcripts. Mb is a heme-protein with 18,8 kDa, highly expressed in skeletal and cardiac muscle, and it belongs to the same family of hemoglobin. About 15% of iron in the body is present in muscle tissue. Thus, this study aimed to investigate if long- and short-term Fe supplementation and restriction affect Mb gene expression in the oxidative Soleus (S), glycolitic Extensorum Digitalis Longus (EDL), and cardiac muscles. It was shown that long- term Fe restriction increased Mb mRNA and protein expression only in S muscle, without interfering in the transcript polyadenylation, whereas Fe supplementation did not alter any parameter evaluated in the three tissues. The short-term iron administration did not change the Mb mRNA, polyadenylation and protein expression in any of the tissues studied. The present results indicate that the regulation of Mb gene expression by iron occurs only at transcriptional level and in a tissue specific manner.

O ferro (Fe) é um oligoelemento capaz de aceitar e doar elétrons. Tal propriedade o torna extremamente útil em diversos componentes importantes ao bom funcionamento do organismo e da célula. O Fe está associado a algumas proteínas, está presente em citocromos, em moléculas que se ligam ao oxigênio (hemoglobina e mioglobina) e em uma grande variedade de enzimas. O aumento e a diminuição da sua oferta levam a alterações na expressão de RNAs mensageiros e proteínas responsáveis pela sua própria homeostase. Sabe-se que a expressão de vários genes envolvidos no metabolismo do Fe é regulada pós-transcricionalmente, por meio de mecanismo que é desencadeado por sua ligação em regiões não traduzíveis presentes em mRNAs específicos, o que interfere no seu grau de poliadenilação, e por conseguinte, na estabilidade e na tradução do transcrito. A Mb é uma heme-proteína de 18,8 kDa, altamente expressa no tecido muscular esquelético e cardíaco, e que pertence a mesma família da hemoglobina. Sabendo-se que cerca de 15% do Fe existente no organismo está presente nos músculos, no presente trabalho avaliamos se a suplementação e restrição de Fe, a curto e longo prazo, alteram a expressão gênica da Mb no músculo oxidativo Soleus (S), glicolítico Extensor Digital Longo (EDL) e no cardíaco. Observamos que a restrição de Fe, a longo prazo, provocou um aumento na expressão gênica e protéica da Mb, apenas no músculo Soleus, sem alterar o grau de poliadenilação do transcrito, enquanto a suplementação não alterou os parâmetros avaliados em nenhum dos tecidos. A administração aguda de Fe não alterou a expressão gênica e protéica da Mb, nem o grau de poliadenilação do transcrito em nenhum dos tecidos estudados. Estes resultados sugerem que a regulação da expressão da Mb pelo Fe se dá apenas transcricionalmente, e de maneira tecido específica. / Iron is a trace element that can accept and donate electrons. This property makes iron extremely important to several components involved with the proper functioning of the organism and cells. Iron is associated with some proteins, is present in cytochromes, molecules that bind to oxygen (hemoglobin and myoglobin) and a variety of enzymes. The increase and decrease of its offer lead to changes in the expression of mRNAs and proteins responsible for their own homeostasis. It is known that the expression of several genes involved in the metabolism of iron is regulated post-transcriptionally through a mechanism that is triggered by its binding in non-translatable regions of specific mRNAs, which interferes with their polyadenylation, and as a consequence, with the stability and translation of the transcripts. Mb is a heme-protein with 18,8 kDa, highly expressed in skeletal and cardiac muscle, and it belongs to the same family of hemoglobin. About 15% of iron in the body is present in muscle tissue. Thus, this study aimed to investigate if long- and short-term Fe supplementation and restriction affect Mb gene expression in the oxidative Soleus (S), glycolitic Extensorum Digitalis Longus (EDL), and cardiac muscles. It was shown that long- term Fe restriction increased Mb mRNA and protein expression only in S muscle, without interfering in the transcript polyadenylation, whereas Fe supplementation did not alter any parameter evaluated in the three tissues. The short-term iron administration did not change the Mb mRNA, polyadenylation and protein expression in any of the tissues studied. The present results indicate that the regulation of Mb gene expression by iron occurs only at transcriptional level and in a tissue specific manner.