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1.
Nat Metab ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789798

RESUMO

The energy cost of neuronal activity is mainly sustained by glucose1,2. However, in an apparent paradox, neurons modestly metabolize glucose through glycolysis3-6, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase-3 (PFKFB3)3,7,8, a key glycolysis-promoting enzyme. To evaluate the in vivo physiological importance of this hypoglycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression. In vivo molecular, biochemical and metabolic flux analyses of these neurons revealed an accumulation of anomalous mitochondria, complex I disassembly, bioenergetic deficiency and mitochondrial redox stress. Notably, glycolysis-mediated nicotinamide adenine dinucleotide (NAD+) reduction impaired sirtuin-dependent autophagy. Furthermore, these mice displayed cognitive decline and a metabolic syndrome that was mimicked by confining Pfkfb3 expression to hypothalamic neurons. Neuron-specific genetic ablation of mitochondrial redox stress or brain NAD+ restoration corrected these behavioural alterations. Thus, the weak glycolytic nature of neurons is required to sustain higher-order organismal functions.

2.
Redox Biol ; 41: 101944, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33780775

RESUMO

Reactive oxygen species (ROS) are a common product of active mitochondrial respiration carried in mitochondrial cristae, but whether cristae shape influences ROS levels is unclear. Here we report that the mitochondrial fusion and cristae shape protein Opa1 requires mitochondrial ATP synthase oligomers to reduce ROS accumulation. In cells fueled with galactose to force ATP production by mitochondria, cristae are enlarged, ATP synthase oligomers destabilized, and ROS accumulate. Opa1 prevents both cristae remodeling and ROS generation, without impinging on levels of mitochondrial antioxidant defense enzymes that are unaffected by Opa1 overexpression. Genetic and pharmacologic experiments indicate that Opa1 requires ATP synthase oligomerization and activity to reduce ROS levels upon a blockage of the electron transport chain. Our results indicate that the converging effect of Opa1 and mitochondrial ATP synthase on mitochondrial ultrastructure regulate ROS abundance to sustain cell viability.


Assuntos
GTP Fosfo-Hidrolases , Membranas Mitocondriais , Trifosfato de Adenosina/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Mitocôndrias , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Kasmera ; 45(1): 8-15, ene.-jun. 2017. ilus
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1008007

RESUMO

La identificación bacteriana durante las infecciones microbiológicas es un aspecto crítico a la hora de escoger un tratamiento específico para evitar complicaciones del paciente o en algunos casos su muerte. Por ello, incrementar el crecimiento celular durante el diagnóstico clínico por cultivo bacteriano puede reducir el tiempo para determinar el patógeno que causa la enfermedad. En este trabajo, se utilizó el cultivo bacteriano como metodología y se evaluó el crecimiento de Staphylococcus aureus en un medio de cultivo convencional enriquecido con extractos de Chenopodium quinoa, Amaranthus caudatus y Salvia hispanica. Los resultados obtenidos muestran que estos extractos, a bajas concentraciones, tienen un efecto protector contra la citotoxicidad que se podría generar por el estrés oxidativo producto del metabolismo celular de las bacterias cultivadas in vitro e incrementan significativamente el crecimiento bacteriano. La adicción de estos extractos a los medios convencionales podría mejorar el crecimiento bacteriano durante un diagnóstico bacteriológico y reducir el tiempo de identificación del patógeno.


Increasing the bacterial growth rate reduces the time getting the bacteria identification. This is helpful to choose an accurate and quick therapeutic strategy during microbiological infections, avoiding illness complications or in some cases the death. Here, we used bacterial growth method and we evaluated the growth of Staphylococcus aureus including an extract of Chenopodium quinoa, Amaranthus caudatus and Salvia hispanica in the routine culture media. Results show that adding these extracts, at low concentrations, have a protective effect against the cytotoxicity that could be generated by the oxidative stress product of the cellular metabolism of the bacteria growing in vitro and significantly increase the bacterial growth. The addition of these extracts to conventional culture media could improve bacterial growth during a bacteriological diagnosis and to reduce the time of pathogen identification.

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