RESUMO
Reduced mechanical loading during bedrest, spaceflight, and casting, causes rapid morphological changes in skeletal muscle: fiber atrophy and reduction of slow-twitch fibers. An emerging signaling event in response to unloading is the translocation of neuronal nitric oxide synthase (nNOSµ) from the sarcolemma to the cytosol. We used EUK-134, a cell-permeable mimetic of superoxide dismutase and catalase, to test the role of redox signaling in nNOSµ translocation and muscle fiber atrophy as a result of short-term (54 h) hindlimb unloading. Fischer-344 rats were divided into ambulatory control, hindlimb-unloaded (HU), and hindlimb-unloaded + EUK-134 (HU-EUK) groups. EUK-134 mitigated the unloading-induced phenotype, including muscle fiber atrophy and muscle fiber-type shift from slow to fast. nNOSµ immunolocalization at the sarcolemma of the soleus was reduced with HU, while nNOSµ protein content in the cytosol increased with unloading. Translocation of nNOS from the sarcolemma to cytosol was virtually abolished by EUK-134. EUK-134 also mitigated dephosphorylation at Thr-32 of FoxO3a during HU. Hindlimb unloading elevated oxidative stress (4-hydroxynonenal) and increased sarcolemmal localization of Nox2 subunits gp91phox (Nox2) and p47phox, effects normalized by EUK-134. Thus, our findings are consistent with the hypothesis that oxidative stress triggers nNOSµ translocation from the sarcolemma and FoxO3a dephosphorylation as an early event during mechanical unloading. Thus, redox signaling may serve as a biological switch for nNOS to initiate morphological changes in skeletal muscle fibers.
Assuntos
Antioxidantes/farmacologia , Elevação dos Membros Posteriores , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Óxido Nítrico Sintase Tipo I/metabolismo , Compostos Organometálicos/farmacologia , Salicilatos/farmacologia , Aldeídos/metabolismo , Animais , Citosol/efeitos dos fármacos , Citosol/enzimologia , Modelos Animais de Doenças , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Glicoproteínas de Membrana/metabolismo , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares Esqueléticas/enzimologia , Fibras Musculares Esqueléticas/patologia , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Fibras Musculares de Contração Lenta/enzimologia , Fibras Musculares de Contração Lenta/patologia , Atrofia Muscular/enzimologia , Atrofia Muscular/patologia , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Fosforilação , Transporte Proteico , Ratos , Ratos Endogâmicos F344 , Sarcolema/efeitos dos fármacos , Sarcolema/enzimologia , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
At the beginning of 1996, we started with a structural periodical screening of babies that were prematurely born. This was done utilizing a protocol that was developed in cooperation with both the author and the Neonatology Department of our hospital in Curacao. After more than 200 screenings only one case of retinopathy of prematurity, stage 3, was detected. (AU)
Assuntos
Humanos , Recém-Nascido , Retinopatia da Prematuridade/epidemiologia , Triagem Neonatal , Antilhas HolandesasRESUMO
The protocol "Early Preventive Visual Screening of Children" has been developed in mutual Cooperation with both the Islands Ophthalmologic Society and the Department of Youth Preventitive Medicine of the Island Health Service. The aim is to periodically screen for function of the visual system in children starting at a very young age and going up to age 15 years. This means that at an early stage, dysfunctional problems can be detected and appropriately dealth with. This protocol has two parts. The first one is about the visual examination and the second part has to do with the visual acuity measurement in children. (AU)
