RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aß) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.

Assuntos

Doença de Alzheimer/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Fosforilação , Proteínas tau/química , Proteínas tau/metabolismo

RESUMO

Infection with Trypanosoma cruzi Chagas, 1909 is reported to increase the production of reactive oxygen species in patients with Chagas disease. Mitochondria dysfunction, host inflammatory response and inadequate antioxidant response are described as the main factors leading to oxidative stress during acute and chronic stages of the disease. The Seahorse XFe24 extracellular flux platform allows energy metabolism determination through mitochondrial respiration and glycolysis measurements. XFe24 platform can be used in in vitro models of T. cruzi-infected cells, which allow the assessment and even modulation of endogenous conditions of infected cells, generating readouts of real-time cellular bioenergetics changes. In this protocol, we standardised the use of XFe24 technology in T. cruzi infected AC16 cardiomyocytes and SGHPL-5 trophoblasts. In addition, we provide a list of optimised assay specifications, advantages and critical steps to be considered during the process. Cardiomyocytes and trophoblasts are attractive target cells to evaluate the metabolic environment in acute, chronic and congenital Chagas transmission scenarios.

Assuntos

Mitocôndrias/parasitologia , Trypanosoma cruzi/fisiologia , Animais , Linhagem Celular , Respiração Celular , Humanos , Camundongos , Mitocôndrias/fisiologia , Miócitos Cardíacos/parasitologia , Miócitos Cardíacos/fisiologia , Espécies Reativas de Oxigênio , Trofoblastos/parasitologia , Trofoblastos/fisiologia

RESUMO

Head and neck squamous cell carcinoma (HNSCC) cells that are positive for human papillomavirus (HPV+) favor mitochondrial metabolism rather than glucose metabolism. However, the involvement of mitochondrial metabolism in HNSCC HPV+ cells is still unknown. The aim of this work was to evaluate the role of E6 oncoproteins from HPV16 and HPV18 in the mitochondrial metabolism in an HNSCC model. We found that E6 from both viral types abates the phosphorylation of protein kinase B-serine 473 (pAkt), which is associated with a shift in mitochondrial metabolism. E6 oncoproteins increased the levels of protein subunits of mitochondrial complexes (I to IV), as well as the ATP synthase and the protein levels of the voltage dependent anion channel (VDAC). Although E6 proteins increased the basal and leak respiration, the ATP-linked respiration was not affected, which resulted in mitochondrial decoupling. This increase in leak respiration was associated to the induction of oxidative stress (OS) in cells expressing E6, as it was observed by the fall in the glutathione/glutathione disulfide (GSH/GSSG) rate and the increase in reactive oxygen species (ROS), carbonylated proteins, and DNA damage. Taken together, our results suggest that E6 oncoproteins from HPV16 and HPV18 are inducers of mitochondrial metabolism.

Assuntos

Proteínas de Ligação a DNA/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Mitocôndrias/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/química , Proteínas Repressoras/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Mitocôndrias/virologia , Papillomaviridae/metabolismo , Células Tumorais Cultivadas

RESUMO

Serum levels of leukotriene-B4 (LTB4) are increased in type 1 diabetes (T1D) and it mediates systemic inflammation and macrophage reprogramming associated with this condition. Herein, we investigated the involvement of LTB4 in adiposity loss, hyperlipidemia, and changes in macrophage metabolism in a mouse model of streptozotocin-induced T1D. LTB4 receptor (BLT1) antagonist u75302 was employed to block LTB4 effects. As expected, hypoinsulinemia in T1D was associated with hyperglycemia, low levels of glucagon, hyperlipidemia, significant body fat loss, and increased white adipose tissue expression of Fgf21, a marker for lipolysis. With the exception of hyperglycemia and hypoglucagonemia, blockade of LTB4 signaling reverted these parameters in T1D mice. Along with hyperlipidemia, macrophages from T1D mice exhibited higher lipid uptake and accumulation. These cells also had enhanced glycolysis and oxidative metabolism and these parameters were dependent on the mitochondrial uncoupling respiration, as evidenced by elevated expression of oxidation markers carnitine palmitoyltransferase and uncoupling protein 1. Interestingly, all these parameters were at least partially reverted in T1D mice treated with u75302. Altogether, these findings suggest that in T1D mice LTB4/BLT1 is involved in the fat loss, hyperlipidemia, and increased macrophage lipid uptake and metabolism with an important involvement of mitochondrial uncoupling activity. These previously unrecognized LTB4/BLT1 functions may be explored in future to therapeutically alleviate severity of hyperlipidemia and systemic inflammation in T1D.

Assuntos

Adiposidade , Diabetes Mellitus Tipo 1/metabolismo , Leucotrieno B4/farmacologia , Macrófagos Peritoneais/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Glicólise/efeitos dos fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo

RESUMO

This article reviews the interactions between nitric oxide (NO) and mitochondrial respiration. Mitochondrial ATP synthesis is responsible for virtually all energy production in mammals, and every other process in living organisms ultimately depends on that energy production. Furthermore, both necrosis and apoptosis, that summarize the main forms of cell death, are intimately linked to mitochondrial integrity. Endogenous and exogenous •NO inhibits mitochondrial respiration by different well-studied mechanisms and several nitrogen derivatives. Instantaneously, low concentrations of •NO, specifically and reversibly inhibit cytochrome c oxidase in competition with oxygen, in several tissues and cells in culture. Higher concentrations of •NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Peroxynitrite can cause opening of the permeability transition pore and opening of this pore causes loss of cytochrome c, which in turn might contribute to peroxynitrite-induced inhibition of respiration. Therefore, the inhibition of cytochrome c oxidase by •NO may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen, which depend on reactive nitrogen species formation, pH, proton motriz force and oxygen supply to tissues.

Assuntos

Respiração Celular/fisiologia , Mitocôndrias/metabolismo , Óxido Nítrico/fisiologia , Animais , Bactérias , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Humanos , Ácido Peroxinitroso/fisiologia , Plantas

RESUMO

Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.

Assuntos

Respiração Celular/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Antioxidantes , Humanos , Estresse Oxidativo , Resveratrol

RESUMO

The intensity of cell respiration is related to the storage potential of a horticultural product. In the case of apples the main modification during storage is the metabolization of organic acids. Mechanical damage is frequent in fruit post harvest handling and the external forces involved can accelerate the respiratory pattern of fruits leading to further losses. The objectives of this work were to evaluate the effects of mechanical damage by impact and compressing on the respiratory pattern of Fuji Suprema and Royal Gala apples. The experiments consisted of five treatments with three repetitions of six fruit each. After the treatment application, fruit were set in closed flasks and maintained in room temperature during the CO2 determination (ml CO2 kg-1 h-1). The measurements were made with a CO2 analyzer equipped with a zircon detector. The readings were taken at 0, 1, 2, 4, 6, 24, 48 e 168 hours after the treatment and data were submitted to a regression analysis. There was an increase in fruit respiration after the treatment application. The respiratory profiles along the evaluated period show increase of the respiratory rate after the treatment application. The greatest increase for most treatments occurred within the first six hours after the treatment, with posterior reduction. The regression curves of the respiratory rate in function of the treatment applied showed the

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A intensidade da respiração celular está relacionada com o potencial de armazenamento nos produtos hortícolas; no caso de maçãs, a principal modificação é a metabolização dos ácidos orgânicos. Danos mecânicos são freqüentes na pós-colheita de frutos, e estas forças externas podem acelerar o padrão respiratório destes, acarretando em perdas posteriores. Os objetivos desse trabalho foram avaliar os efeitos de danos mecânicos por impactos e compressões sobre o padrão respiratório de maçãs Fuji Suprema e Royal Gala. Os experimentos consistiram de cinco tratamentos com três repetições e seis frutos por repetição. Após a aplicação dos tratamentos, os frutos foram colocados em frascos vedados, mantidos à temperatura ambiente onde foram realizadas as determinações do CO2 (ml CO2 kg-1 h-1) com analisador equipado com detector de zircônio. As leituras ocorreram a 0, 1, 2, 4, 6, 24, 48 e 168 horas após a instalação e os dados foram submetidos à análise de regressão. Houve um aumento da respiração após a aplicação dos tratamentos. O maior incremento, para maior parte dos tratamentos, foi observado nas primeiras seis horas, com posterior redução nas taxas de respiração após 24 horas. As curvas de regressão da intensidade respiratória em função dos tratamentos evidenciam que o incremento nas taxas respiratórias está associado com a intensidade das forças mecânicas aplicadas. Os incrementos n

RESUMO

The intensity of cell respiration is related to the storage potential of a horticultural product. In the case of apples the main modification during storage is the metabolization of organic acids. Mechanical damage is frequent in fruit post harvest handling and the external forces involved can accelerate the respiratory pattern of fruits leading to further losses. The objectives of this work were to evaluate the effects of mechanical damage by impact and compressing on the respiratory pattern of Fuji Suprema and Royal Gala apples. The experiments consisted of five treatments with three repetitions of six fruit each. After the treatment application, fruit were set in closed flasks and maintained in room temperature during the CO2 determination (ml CO2 kg-1 h-1). The measurements were made with a CO2 analyzer equipped with a zircon detector. The readings were taken at 0, 1, 2, 4, 6, 24, 48 e 168 hours after the treatment and data were submitted to a regression analysis. There was an increase in fruit respiration after the treatment application. The respiratory profiles along the evaluated period show increase of the respiratory rate after the treatment application. The greatest increase for most treatments occurred within the first six hours after the treatment, with posterior reduction. The regression curves of the respiratory rate in function of the treatment applied showed the

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A intensidade da respiração celular está relacionada com o potencial de armazenamento nos produtos hortícolas; no caso de maçãs, a principal modificação é a metabolização dos ácidos orgânicos. Danos mecânicos são freqüentes na pós-colheita de frutos, e estas forças externas podem acelerar o padrão respiratório destes, acarretando em perdas posteriores. Os objetivos desse trabalho foram avaliar os efeitos de danos mecânicos por impactos e compressões sobre o padrão respiratório de maçãs Fuji Suprema e Royal Gala. Os experimentos consistiram de cinco tratamentos com três repetições e seis frutos por repetição. Após a aplicação dos tratamentos, os frutos foram colocados em frascos vedados, mantidos à temperatura ambiente onde foram realizadas as determinações do CO2 (ml CO2 kg-1 h-1) com analisador equipado com detector de zircônio. As leituras ocorreram a 0, 1, 2, 4, 6, 24, 48 e 168 horas após a instalação e os dados foram submetidos à análise de regressão. Houve um aumento da respiração após a aplicação dos tratamentos. O maior incremento, para maior parte dos tratamentos, foi observado nas primeiras seis horas, com posterior redução nas taxas de respiração após 24 horas. As curvas de regressão da intensidade respiratória em função dos tratamentos evidenciam que o incremento nas taxas respiratórias está associado com a intensidade das forças mecânicas aplicadas. Os incrementos n