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Mol Cell Endocrinol ; 533: 111335, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052303

RESUMO

People with obesity are often dyslipidemic and prescribed statins to prevent cardiovascular events. A common side effect of statin use is myopathy. This could potentially be caused by the reduction of selenoproteins that curb oxidative stress, in turn, affecting creatine metabolism. We determined if statins regulate hepatic and muscular selenoprotein expression, oxidative stress and creatine metabolism. Mice lacking selenocysteine lyase (Scly KO), a selenium-provider enzyme for selenoprotein synthesis, were fed a high-fat, Se-supplemented diet and treated with simvastatin. Statin improved creatine metabolism in females and oxidative responses in both sexes. Male Scly KO mice were heavier than females after statin treatment. Hepatic selenoproteins were unaffected by statin and genotype in females. Statin upregulated muscular Gpx1 in females but not males, while Scly loss downregulated muscular Gpx1 in males and Selenon in females. Osgin1 was reduced in statin-treated Scly KO males after AmpliSeq analysis. These results refine our understanding of the sex-dependent role of selenium in statin responses.


Assuntos
Fígado/metabolismo , Liases/genética , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Selenoproteínas/metabolismo , Sinvastatina/administração & dosagem , Animais , Creatinina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Selênio , Caracteres Sexuais , Sinvastatina/farmacologia , Glutationa Peroxidase GPX1
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