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1.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339064

RESUMO

Proteinaceous aggregates accumulate in neurodegenerative diseases such as Alzheimer's Disease (AD), inducing cellular defense mechanisms and altering the redox status. S100 pro-inflammatory cytokines, particularly S100B, are activated during AD, but recent findings reveal an unconventional molecular chaperone role for S100B in hindering Aß aggregation and toxicity. This suggests a potential protective role for S100B at the onset of Aß proteotoxicity, occurring in a complex biochemical environment prone to oxidative damage. Herein, we report an investigation in which extracellular oxidative conditions are mimicked to test if the susceptibility of S100B to oxidation influences its protective activities. Resorting to mild oxidation of S100B, we observed methionine oxidation as inferred from mass spectrometry, but no cysteine-mediated crosslinking. Structural analysis showed that the folding, structure, and stability of oxidized S100B were not affected, and nor was its quaternary structure. However, studies on Aß aggregation kinetics indicated that oxidized S100B was more effective in preventing aggregation, potentially linked to the oxidation of Met residues within the S100:Aß binding cleft that favors interactions. Using a cell culture model to analyze the S100B functions in a highly oxidative milieu, as in AD, we observed that Aß toxicity is rescued by the co-administration of oxidized S100B to a greater extent than by S100B. Additionally, results suggest a disrupted positive feedback loop involving S100B which is caused by its oxidation, leading to the downstream regulation of IL-17 and IFN-α2 expression as mediated by S100B.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Estresse Oxidativo , Agregados Proteicos , Oxirredução , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo
2.
Ir J Med Sci ; 192(4): 1835-1845, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36224463

RESUMO

BACKGROUND: In humans, zinc is involved in many biological functions acting as signaling ion, neurotransmitter, structural component of proteins, and cofactor for many enzymes and, through this, is an important regulator of the immune and nervous system. Food supplies zinc to the human body, but a high prevalence of inadequate dietary zinc intake has been reported worldwide. AIMS: The objective of this study was to investigate the zinc intake and bioavailability of over 250 women (pregnant and non-pregnant) based in Ireland, in order to evaluate the dietary inadequacy of zinc. METHODOLOGY: We used a food frequency questionnaire designed to assess the zinc intake and bioavailability of the participants. RESULTS: Our results show that 58% of participants are at risk of inadequate zinc intake and that 29% may be zinc deficient. The prevalence of inadequate zinc intake was lower for pregnant women (zinc deficient 9%, at risk 38%) than for non-pregnant women due to more frequent consumption of supplements. Low zinc intake was not correlated with the age of participants and resulted from a combination of inadequate intake of zinc-rich food and relatively higher intake of food items rich in phytate, a major zinc uptake inhibitor. CONCLUSIONS: We conclude that at present, low zinc intake may be prevalent in as much as 87% of women, including 47% of pregnant women. Therefore, zinc status needs to be considered as a factor impacting the health of women, and in particular pregnant women, also in industrialized and developed countries such as Ireland.


Assuntos
Desnutrição , Zinco , Feminino , Humanos , Zinco/análise , Prevalência , Irlanda/epidemiologia , Dieta , Estado Nutricional
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