RESUMO
Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity.
Assuntos
Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/fisiologia , Animais , Morte Celular/fisiologia , Humanos , Doenças Neurodegenerativas/prevenção & controle , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Selênio/metabolismoRESUMO
PURPOSE: To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. METHODS: CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 µg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months. RESULTS: In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. CONCLUSIONS: Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.
Assuntos
Autoimunidade/efeitos dos fármacos , Suplementos Nutricionais , Glutationa Peroxidase/genética , Iodeto Peroxidase/imunologia , Selenometionina/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Tireoidite Autoimune/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Genótipo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Selenometionina/administração & dosagem , Glândula Tireoide/imunologia , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologia , Resultado do Tratamento , Adulto Jovem , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: There is equivocal evidence about beneficial properties of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) for older adults. OBJECTIVE: This study investigated the relationship between circulating ω-3 LCPUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels and their corresponding dietary intakes with cognition and physical function in a cohort of community-dwelling older adults at risk of dementia. METHODS: A cross-sectional analysis was conducted among 142 community-dwelling older adults (60-85 years) with subjective memory complaints. Erythrocyte fatty acids (ω-3 LCPUFA) and the omega-3 index were measured; dietary DHA and EPA were assessed with a LCPUFA specific questionnaire. Cognition was measured using the Cogstate computerised battery and Trail-making tests. Muscle strength was assessed by grip strength and physical function via the four-square step test, 30-second sit-to-stand, timed up-and-go test, and 4-m walk test. Multiple regression analysis was used to assess the relationship between erythrocyte ω-3 LCPUFA, dietary intake, cognitive and physical function. RESULTS: Higher dietary DHA and EPA were associated with better global cognitive function (DHA: ß=0.164, p=0.042; EPA: ß=0.188, p=0.020). Higher dietary EPA was associated with better attention/psychomotor composite scores (ß=0.196, p=0.024), mobility (four-square step test: ß=-0.202, p=0.015) and gait speed (4m walk test: ß=-0.200, p=0.017). No associations were found between erythrocyte ω-3 LCPUFA and cognitive or functional performance measures. CONCLUSIONS: In community-dwelling older adults with subjective memory complaints, higher dietary ω-3 LCPUFA intake was associated with better cognitive and physical function, supporting the evidence that ω-3 fatty acids play a role in optimising physical and cognitive health during ageing.