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1.
JCI Insight ; 5(4)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32017711

RESUMO

The mitochondrial calcium uniporter is widely accepted as the primary route of rapid calcium entry into mitochondria, where increases in matrix calcium contribute to bioenergetics but also mitochondrial permeability and cell death. Hence, regulation of uniporter activity is critical to mitochondrial homeostasis. The uniporter subunit EMRE is known to be an essential regulator of the channel-forming protein MCU in cell culture, but EMRE's impact on organismal physiology is less understood. Here we characterize a mouse model of EMRE deletion and show that EMRE is indeed required for mitochondrial calcium uniporter function in vivo. EMRE-/- mice are born less frequently; however, the mice that are born are viable, healthy, and do not manifest overt metabolic impairment, at rest or with exercise. Finally, to investigate the role of EMRE in disease processes, we examine the effects of EMRE deletion in a muscular dystrophy model associated with mitochondrial calcium overload.


Assuntos
Canais de Cálcio/fisiologia , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Coração/fisiopatologia , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Traumatismo por Reperfusão Miocárdica/metabolismo
2.
J Biomed Opt ; 21(9): 091302, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27050534

RESUMO

Near-infrared spectroscopy (NIRS) has been used to measure reactive hyperemia following a vascular occlusion. However, the procedures and methods of analysis used have varied. The purpose of the present study is to identify reproducible methods for measuring reactive hyperemia using HbO2 NIRS signals in the calf and foot. Healthy participants (10 male, 10 female) aged 19 to 28 years performed one of two tests: reproducibility trials or elevation protocol (30 and 60 cm limb elevation above the heart). The time to 50% reperfusion (T1/2) and the second (R2q) quartile rates of reperfusion were found to be the most reproducible parameters (coefficient of variation= 7.12 to 14.1%). The time to 95% reperfusion (T95) was 12.7% more reproducible on average than the previously reported parameter of time to peak hyperemia. Measures of reperfusion time and rate slowed with increasing limb elevation. Correlations were identified between the calf and foot in the measurements of R2q (R2 = 0.713, p = 0.021), T1/2 (R2 = 0.673, p = 0.033), and T95 (R2 = 0.792, p = 0.006). Half and 95% recovery times and second and third quartile rates expressed good reproducibility and sensitivity to change with reduced perfusion pressure. NIRS measures of reactive hyperemia have the potential to evaluate microvascular perfusion in clinical populations.


Assuntos
Hiperemia/diagnóstico por imagem , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Adulto Jovem
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