Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.

The relieving effect of sun-dried protein tonic on sports fatigue / O efeito calmante na fadiga esportiva da proteína tônica secada ao sol / El efecto calmante en la fatiga deportiva de la proteína tónica secada al sol

ABSTRACT Fatigue is a comprehensive process that involves many physiological and biochemical factors. It is a normal physiological reaction when human physical or mental activities reach a certain level. In recent years, it has been verified that free radicals are closely related to exercise-induced fatigue. Cardamine bursa purified selenoprotein has good oxygen-free radical scavenging ability and anti-lipid peroxide. It could protect mitochondria, liver, and red blood cells from peroxide injury. Therefore, it was speculated that the purification of selenoprotein Cardamine may play an active role in attenuating exercise-induced fatigue by scavenging free radicals. This study cleared the selenite protein Capsella bursa (SPC) as a research object, and evaluated its structural characteristics in relieving exercise-induced fatigue. The selenoprotein index system for exercise-induced fatigue was constructed by combining two AHP methods, principal component analysis and factor analysis. Purity, subunit composition, amino acid composition and RCM content were evaluated. The corresponding RCM protein was preliminarily predicted. The results showed that SPCH could significantly prolong the swimming time (P <0.01), improve the lactate clearance capacity (P <0.01), increase the glycogen content of the liver (P <0.01), and reduce the level of the BUN (P <0.05). SPCH has a good effect in relieving exercise-induced fatigue in mice, so it can be considered for development as a nutritional supplement to alleviate exercise-induced fatigue.

RESUMO Fadiga é um processo abrangente envolvendo muitos fatores fisiológicos e bioquímicos. É uma reação fisiológica normal quando as atividades físicas ou mentais humanas atingem um certo nível. Nos últimos anos, verificou-se que os radicais livres estão intimamente relacionados com a fadiga induzida pelo exercício. A selenoproteina purificada de Cardamina bursa tem boa capacidade de depuração de radicais sem oxigénio e de peróxido anti-lípido. Poderia proteger as mitocôndrias, fígado e glóbulos vermelhos de lesões por peróxido. Por conseguinte, especulou-se que a purificação da selenoproteina de Cardamina pode desempenhar um papel activo na atenuação da fadiga induzida pelo exercício por meio de radicais livres de scavenging. Este estudo depurou a proteína selenita Capsella bursa (SPC) como objeto de pesquisa, e avaliou as suas características estruturais no alívio da fadiga induzida pelo exercício. O sistema de índice de selenoproteinas para a fadiga induzida pelo exercício foi construído por meio da combinação dos métodos de AHP, análise principal de componentes e a análise de fatores. Foram avaliados a pureza, a composição sub-unitária, a composição de aminoácidos e o conteúdo do RCM. A proteína correspondente do RCM foi prevista preliminarmente. Os resultados mostraram que o SPCH poderia prolongar significativamente o tempo de natação (P < 0.01), melhorar a capacidade de depuração do lactato (P< 0.01), aumentar o conteúdo do glicogênio do fígado (P < 0.01), e reduzir o nível do BUN (P< 0.05). o SPCH tem um bom efeito em aliviar a fadiga induzida pelo exercício em ratos, de modo que pode ser considerado para desenvolvê-lo como um suplemento nutricional para aliviar a fadiga induzida pelo exercício.

RESUMEN La fatiga es un proceso abarcador que envuelve muchos factores fisiológicos y bioquímicos. Es una reacción fisiológica normal cuando las actividades físicas o mentales humanas alcanzan un cierto nivel. En los últimos anos, se verificó que los radicales libres están íntimamente relacionados con la fatiga inducida por el ejercicio. La selenoproteína purificada de Cardamina bursa tiene buena capacidad de depuración de radicales sin oxígeno y de peróxido antilipídico. Podría proteger las mitocondrias, el hígado y los glóbulos rojos de lesiones por peróxido. Por consiguiente, se especuló que la purificación de la selenoproteína de Cardamina puede desempeñar un papel activo en la atenuación de la fatiga inducida por el ejercicio por medio de radicales libres de scavenging. Este estudio depuró la proteína selenita Capsella bursa (SPC) como objeto de investigación, y evaluó sus características estructurales en el alivio de la fatiga inducida por el ejercicio. El sistema de índice de selenoproteínas para a fatiga inducida por el ejercicio fue construido por medio de la combinación dos métodos de AHP, el análisis principal de componentes y el análisis de factores. Fueron evaluados la pureza, la composición sub-unitaria, la composición de aminoácidos y el contenido del RCM. La proteína correspondiente del RCM fue prevista preliminarmente. Los resultados mostraron que el SPCH podría prolongar significativamente el tiempo de natación (P < 0.01), mejorar la capacidad de depuración del lactato (P< 0.01), aumentar el contenido del glicógeno del hígado (P < 0.01), y reducir el nivel del BUN (P< 0.05). el SPCH tiene un buen efecto en aliviar la fatiga inducida por el ejercicio en ratones, de modo que puede ser considerado para desarrollarlo como un suplemento nutricional para aliviar la fatiga inducida por el ejercicio.

Nutrigenômica como ferramenta preventiva de doenças crônicas não transmissíveis / Nutrigenomics as a preventive tool for chronic non-communicable diseases / NUTRIGENOMICS AS A PREVENTIVE TOOL FOR CHRONIC NON-COMMUNICABLE DISEASES

A nutrigenômica representa uma ciência emergente que estuda a relação entre os nutrientes e os genes humanos. Dessa forma, as necessidades de alimentos, compostos bioativos e nutrientes variam entre os indivíduos, por conta dos polimorfismos gênicos, principalmente os de nucleotídeo único, podendo resultar no desenvolvimento de diversas doenças crônicas não transmissíveis (DCNTs). Este artigo objetiva conhecer as mais recentes informações sobre a nutrigenômica e os principais polimorfismos genéticos relacionados às DCNTs, bem como o impacto dos nutrientes na modulação da expressão gênica e prevenção destas patologias. Para o levantamento bibliográfico, optou-se pela busca de artigos nas bases de dados PubMed e SciELO, nos idiomas Português e Inglês. Aplicou-se a combinação dos seguintes descritores: "nutrigenômica e necessidades nutricionais", "nutrigenômica e obesidade", "nutrigenômica e diabetes mellitus tipo 2", "nutrigenômica e câncer" e "nutrigenômica e doença inflamatória intestinal". Evidências indicam que diversos tipos de polimorfismos estão associados à incidência, progressão e gravidade de doenças como a obesidade, diabetes mellitus tipo 2 (DM2), câncer e doenças inflamatórias intestinais (DIIs). Os principais polimorfismos encontrados que se relacionam com as DCNTs são: rs9939609 do fat mass and obesity associated (FTO), rs174547 do Fatty acid desaturase 1 (FADS1), Gln27Glu do receptor ß-adrenérgico 2 (ADRB2), Lys656Asn do receptor de leptina (LEPR), -174C/G da interleucina 6 (IL-6), Pro12Ala do receptor ativado por proliferador de peroxissoma gama 2 (PPAR-gama2), rs4315495 da lipina 1 (LPIN1), rs266729 no gene da adiponectina, rs10920533 em adiponectina receptor 1 (AdipoR1), Pro12Ala do receptor ativado por proliferador de peroxissoma γ (PPARγ), rs1440581 da Protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K), alelo G para o polimorfismo -11377C>G, alelo A para o polimorfismo 11391 G>A, Cdx2 do receptor de vitamina D (RVD), genes de selenoproteínas sob baixas concentrações de selênio (DIO1, DIO2, GPX-1, GPX-3, SEPHS1, SEPSECS e TXNRD2) e alelo G do rs12212067 do Forkhead box O3 (FOXO3). É fundamental entender as interações gene-nutriente nestas doenças e as diferentes respostas metabólicas envolvidas, para que assim se possa orientar a alimentação de cada indivíduo conforme a sua herança genética. Enfim, os estudos não são conclusivos sobre o papel de cada fator na alteração dos genes, e a nutrigenômica é um fator importante e complexo que precisa avançar com a ciência nutricional.

Nutrigenomics represents an emerging science that studies the relation between nutrients and the human genes. Thus, the need for food, bioactive composts and nutrients vary from person to person due to genic polymorphisms, mainly single nucleotide polymorphism, which can result in the developing of many Chronic Non-Communicable Diseases (NCDs). This article aims at making a scientific literature review regarding the most recent information on nutrigenomics and the main polymorphisms related to the NCDs, as well as the impact of nutrients on the modulation of the genic expression and prevention of those pathologies. For the literature survey, a search was performed in PubMed and SciELO databases, in Portuguese and English using the combination of the following descriptors: "nutrigenomics and nutritional requirements", "nutrigenomics and obesity", "nutrigenomics and diabetes mellitus, type 2", "nutrigenomics and cancer", and "nutrigenomics and inflammatory bowel disease". Evidence has shown that many types of polymorphisms are associated with the incidence, progression and severity of diseases such as obesity, type 2 diabetes mellitus (T2DM), cancer, and inflammatory bowel diseases (IBD). The main polymorphisms found to be related to NCDs are: rs9939609 of the fat mass and obesity associated (FTO), rs174547 of the fatty acid desaturase 1 (FADS1), Gln27Glu of the ß-adrenergic receptor 2 (ADRB2), Lys656Asn of the leptin receptor (LEPR), -174 G/C of the interleukin-6 (IL-6), Pro12Ala of the peroxisome proliferator-activated receptor gamma 2 (PPAR-gama2), rs4315495 of lipin 1 (LPIN1), rs266729 in the adiponectin gene, rs10920533 in adiponectin receptor 1 (AdipoR1), Pro12Ala of Peroxisome proliferator-activated receptor γ (PPARγ), rs1440581 of Protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K), G allele of the -11377C>G polymorphism, allele A of the 11391 G>A polymorphism, Cdx2 of the vitamin D receptor (VDR), selenoprotein genes under low selenium concentrations (DIO1, DIO2, GPX-1, GPx-3, SEPHS1, SEPSECS and TXNRD2), and G allele of the Forkhead box O3 (FOXO3) rs12212067. It is fundamental to understand the interaction between gene-nutrients in these diseases and the different metabolic answers involved to guide the eating habits of each person according to their genetic heritage. Finally, the studies are not conclusive on the role of each factor in the alteration of the genes, and nutrigenomics is an important and complex factor that needs to advance with nutritional science.

Efeitos do consumo de castanha-do-brasil ( Bertholetia excelsa H. B. K. ) sobre o estresse oxidativo em pacientes com comprometimento cognitivo leve e a relação com variações em genes de selenoproteínas / Effects of the intake of Brazil nut (Bertholetia excels H. B. K) on the oxidative stress in patients with mild cognitive impairment and its relation with polymorphisms in selenoprotein genes

Visto que o estresse oxidativo está intimamente relacionado com a progressão da demência, este se apresenta como um possível alvo terapêutico a fim de preservar as funções cognitivas. No mesmo sentido, estudos mostram o papel antioxidante do selênio, mineral que atua por meio das selenoproteínas, com destaque para a família de enzimas antioxidantes glutationa peroxidase (GPx) e a selenoproteína responsável pelo transporte de selênio, a selenoproteína P (SePP). Entretanto, diferentes genótipos dos genes que codificam essas selenoproteínas podem refletir em diferentes respostas diante de intervenções alimentares. Assim, este trabalho teve como objetivo verificar os efeitos da suplementação com castanha-do-brasil sobre o estresse oxidativo em pacientes com comprometimento cognitivo leve (CCL) e verificar sua relação com os polimorfismos rs1050450 (Pro198Leu) no gene da GPx1, rs3877899 e rs7579 no gene da selenoproteína P. Participaram do estudo 31 indivíduos com CCL, voluntários, de ambos os sexos, frequentadores do Ambulatório de Memória do Idoso do Serviço de Geriatria da Faculdade de Medicina da Universidade de São Paulo, com idade igual ou superior a 60 anos, que foram distribuídos aleatoriamente entre os grupos Castanha e Controle. O grupo Castanha recebeu uma unidade de castanha-do-brasil por dia durante seis meses. Foram avaliados os seguintes marcadores: determinação de selênio no plasma e nos eritrócitos, atividade da GPx eritrocitária, avaliação dos níveis de oxygen radical absorbance capacity (ORAC) e de malondialdeído (MDA) plasmáticos, perfil lipídico sérico e expressão gênica de GPx1 e SePP. Além disso, os participantes foram submetidos à avaliação cognitiva e genotipados quanto aos polimorfismos rs1050450, rs3877899 e rs7579. Cada unidade de castanha-do-brasil forneceu 288,75µg de selênio. Dentre os 31 participantes selecionados, apenas 20 concluíram o estudo, e observou-se que, antes da intervenção, os grupos de estudo não apresentavam diferença quanto aos níveis de selênio no plasma e no eritrócito, bem como na atividade da GPx e nos níveis plasmáticos de ORAC e de MDA. Porém, após a suplementação, verificou-se aumento significativo no selênio plasmático (290,6±74,6) e eritrocitário (574,6±181,4) e na atividade da GPx (59,55±20,79) no grupo Castanha, diferente do grupo Controle (47,48±11,7 no plasma; 33,5±16,1 no eritrócito; 42,54±13,05 atividade da GPx). Em relação ao MDA, verificou-se que ambos os grupos apresentaram aumento após a intervenção, porém não significativo. No caso do ORAC, não se verificou alteração entre os grupos após os seis meses. O escore CERAD, que avalia desempenho cognitivo, não foi diferente entre os grupos após o tratamento, entretanto as mudanças observadas na fluência verbal e na praxia construtiva ao longo do acompanhamento foram mais favoráveis no grupo Castanha. A frequência dos genótipos de referência foram 40% para Pro198Leu, 55% para rs7579 e 60% para rs3877899. Não foram identificadas diferenças entre os níveis de selênio, de atividade da GPx, de MDA e de ORAC entre os genótipos, porém em análise multivariada verificou-se que o alelo variante do Pro198Leu se relacionou com aumento de 0,613 dp na concentração de selênio no plasma no baseline. A influência dos polimorfismos na resposta à intervenção com castanha-do-brasil foi avaliada nos 11 participantes do grupo Castanha, e observou-se que os genótipos não influenciaram na resposta quanto os níveis de selênio plasmático e eritrocitário, bem como de MDA. Entretanto, quanto à atividade da GPx, embora todos os genótipos tenham apresentado aumento após a intervenção, isso não foi significativo para o genótipo dominante do rs7579 e para o variante do rs3877899. A expressão de GPx1 e de SePP também foi diferente entre os genótipos: indivíduos com alelo variante do Pro198Leu apresentaram redução da expressão da GPx1, enquanto carreadores do genótipo homozigoto dominante tiveram aumento. Também percebeu-se que a expressão da SePP foi reduzida em todos os genótipos, entretanto essa mudança foi mais relevante para os genótipos variantes do Pro198Leu e rs7579 e para o genótipo GG do rs3877899. A partir desses resultados, concluiu-se que o consumo de apenas uma castanha-do-brasil diariamente, durante seis meses, é suficiente para recuperar o estado nutricional relativo ao selênio, e isso parece ter efeitos positivos sobre a cognição em idosos com CCL. Além disso, observou-se que o polimorfismo Pro198Leu no gene da GPx1 parece influenciar o estado nutricional quanto ao selênio, bem como a expressão de GPx, enquanto que os polimorfismos rs7579 e rs3877899 parecem não influenciar, de maneira significativa, o metabolismo de selênio frente ao consumo de castanha-do-brasil

Since oxidative stress is closely related to progression of dementia, the antioxidant system may be a potential therapeutic target to preserve cognitive function. In this way, studies show the antioxidant role of selenium, which plays as selenoproteins especially glutathione peroxidase (GPx) family and selenoprotein P (SePP). However, different genotypes of selenoprotein genes may result in different response to dietary intake. Therefore, this work aimed to verify the effects of Brazil nuts intake on oxidative stress and the role of the polymorphisms rs1050450 (Pro198Leu) in GPx1 gene and rs7579 and rs3877899 in SePP gene in mild cognitive impairment (MCI) patients. Study subjects comprised 31 voluntary patients with MCI who attended the Memory and Aging Unit of the Geriatrics Division, University of São Paulo Medical School (Brazil). They were randomly assigned to ingestion of Brazil nuts or to the control group. Brazil nuts group received one nut daily during six months. The following parameters were analysed: selenium concentration in plasma and erythrocyte, GPx activity in erythrocyte, plasmatic levels of oxygen radical absorbance capacity (ORAC) and of malondialdedyde (MDA), serum lipid profile. Besides, we evaluated cognitive performance and the patients were genotyped to rs1050450, rs3877899 e rs7579 polymorphisms. Each Brazil nut provided 288.75µg of selenium. Among 31 enrolled participants, only 20 finished the study. No differences regarding selenium levels, GPx activity, ORAC and MDA levels were observed at baseline between groups. However, after treatment, we observed significant increase in selenium in plasma (290.6±74.6) and in erythrocyte (574.6±181.4) and in GPx activity (59.55±20.79) in treated group, unlike control group (47.48±11.70 selenium in plasma; 33.5±16.1 selenium in erythrocyte; 42.54±13.05 GPx activity). Although not significant, MDA level increased after 6 months in both groups and ORAC levels were not different across time. CERAD total score was not different across time between groups, however changes in verbal fluency and constructional praxis subtests across time were significantly more favorable on the supplemented group when compared with control group. The frequency of dominant genotypes for Pro198Leu, rs7579 and rs3877899 were 40%, 55% and 60%, respectively. We did not observe differences regarding to selenium ORAC and MDA levels and GPx activity among genotypes, however after linear regression analysis the presence of variant allele of Pro198Leu was associated with an increase of 0.613 SD in selenium plasma level at baseline. The effect of polymorphisms in response to Brazil nut intake was analysed in Brazil nut group, and we observed that sele nium and MDA levels were not affected by polymorphisms. However although GPx activity increased in all genotype groups, this was not significant in dominant genotype of rs7579 and variant genotypes of rs3877899. GPx1 and SePP expression was also different among groups across time: variant allele of Pro198Leu presented decreased expression of GPx1 while dominant homozygous presented increase of expression. We also observed that SePP expression was reduced in all genotypes, but his was more important in variant genotypes of Pro198Leu and rs7579 and in GG genotype of rs3877899. From these results, we can conclude that consumption of only one Brazil nut is enough to restore selenium status, and this may be positive effects on cognition performance. Furthermore we observed that Pro198Leu polymorphism may influence selenium nutritional status and GPx activity whereas rs7579 and rs3877899 polymorphisms did not have an effect on selenium metabolism after Brazil nut intake

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

BACKGROUND: Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS: We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS: Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). CONCLUSION: Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

The crustacean selenoproteome similarity to other arthropods homologs: a mini review

Selenoproteins (Sels) are involved in oxidative stress regulation. Glutathione peroxidase (GPx) and thioredoxin reductase are among the most studied Sels in crustaceans. Since their expressions and activities are affected by pathogens, environmental and metabolic factors, their functions might be key factors to orchestrate the redox cellular balance. The most studied invertebrate selenoproteome is from Drosophila. In this fly, SelD and SelB are involved in selenoproteins synthesis, whereas SelBthD, SelH and SelK are associated with embryogenesis and animal viability. None of the Sels found in Drosophila have been identified in marine crustaceans yet, and their discovery and function identification is an interesting research challenge. SelM has been identified in crustaceans and is differentially expressed in tissues, while its function remains to be clarified. SelW and G-rich Sel were recently discovered in marine crustaceans and their functions are yet to be clearly defined. To fully understand the crustacean selenoproteome, it is still necessary to identify important Sels such as the SelD, SelBthD and SelB homologs. This knowledge can also be useful for marine crustacean industry to propose better culture strategies, enhanced health and improved profits.

Selenoprotein S Suppression Enhances the Late Stage Differentiation of Proerythrocytes Via SIRT1

Selenoprotein S (SelS) is widely expressed in diverse tissues where it localizes in the plasma membrane and endoplasmic reticulum. We studied the potential function of SelS in erythrocyte differentiation using K562 cells stably overexpressing SelS wild-type (WT) or one of two SelS point mutants, U188S or U188C. We found that in the K562 cells treated with 1 microM Ara-C, SelS gradually declined over five days of treatment. On day 4, intracellular ROS levels were higher in cells expressing SelS-WT than in those expressing a SelS mutant. Moreover, the cell cycle patterns in cells expressing SelS-WT or U188C were similar to the controls. The expression and activation of SIRT1 were also reduced during K562 differentiation. Cells expressing SelS-WT showed elevated SIRT1 expression and activation (phosphorylation), as well as higher levels of FoxO3a expression. SIRT1 activation was diminished slightly in cells expressing SelS-WT after treatment with the ROS scavenger NAC (12mM), but not in those expressing a SelS mutant. After four days of Ara-C treatment, SelS-WT-expressing cells showed elevated transcription of beta-globin, gamma-globin, epsilon-globin, GATA-1 and zfpm-1, whereas cells expressing a SelS mutant did not. These results suggest that the suppression of SelS acts as a trigger for proerythrocyte differentiation via the ROS-mediated downregulation of SIRT1.

O papel das selenoproteínas no câncer / The role of selenoproteins in cancer

Evidências têm demonstrado que distúrbios do metabolismo são comuns em células tumorais, levando ao aumento do estresse oxidativo. A elevação na produção de espécies reativas de oxigênio (EROs) associada à baixa atividade antioxidante tem sido relacionada a vários tipos de câncer. O selênio, micronutriente antioxidante, pode funcionar como um agente antimutagênico, prevenindo transformações malignas de células normais. Realizou-se um levantamento bibliográfico no período 2000 a 2009 mediante consulta à base de dados PubMed (National Library of Medicine´s Medline Biomedical Literature, USA), selecionando-se 39 artigos que avaliaram a relação entre câncer, estresse oxidativo e suplementação com selênio. O efeito protetor desse mineral é especialmente associado à sua presença na glutationa peroxidase e na tioredoxina redutase, enzimas protetoras do DNA e outros componentes celulares contra o dano oxidativo causado pelas EROs. Vários estudos têm demonstrado a expressão reduzida destas enzimas em diversos tipos de câncer, principalmente quando associados a uma baixa ingestão de selênio, que pode acentuar os danos causados. A suplementação de selênio parece ocasionar redução do risco de alguns tipos de câncer diminuindo o estresse oxidativo e o dano ao DNA. No entanto, mais estudos são necessários para esclarecer as doses de selênio adequadas para cada situação (sexo, localização geográfica e tipo de câncer).

There are evidences that metabolic disorders are common in tumoral cells, leading to increased oxidative stress. The rising in the production of reactive oxygen species associated to low antioxidant activity have been associated to different types of cancer. Selenium, an antioxidant micronutrient can work as an anti-cancer agent preventing malignant modification in healthy cells. A literature review was carried out in the period 2000-2009 in the database PubMed selecting 39 articles which assessed the relationship between cancer, oxidative stress, and supplementation with selenium. The protective effect of selenium is specially associated to the presence of glutathione peroxidase and of thioredoxin reductase enzymes and with other cell components which protect the tissues against the oxidative damage caused by reactive oxygen species - ROS. Several studies have shown a decrease of these enzymes in many types of cancer, mainly when associated with low selenium consumption, increasing the damage caused by ROS. Selenium supplementation seems to reduce the risk of some types of cancer by stress oxidative reduction and by limiting the damage to DNA. Nevertheless, more studies are necessary to clarify the adequate selenium doses in each situation (gender, geographic localization and type of cancer).

Association of SelS mRNA expression in omental adipose tissue with Homa-IR and serum amyloid A in patients with type 2 diabetes mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tanis was reported as a putative receptor for serum amyloid A (SAA) involving glucose regulated protein in insulin regulated resistance. It was found to be dysregulated in diabetic rats (Psammomys obesus, Israeli sand rat) and its homologue for humans is SelS/AD-015. The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus (T2DM), and age- and weight-matched nondiabetic patients, the relationship of SelS mRNA with Homa-IR and serum SAA level.</p><p><b>METHODS</b>Human omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction (PCR), Homa-IR estimated by standard formula and SAA level by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>SelS mRNA expression, Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabetic control group. SelS mRNA level was positively correlated with Homa-IR and SAA level in each group.</p><p><b>CONCLUSIONS</b>SelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis.</p>

The apoptosis-inducing activity of human selenoprotein P shorter isoform / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Human selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA, which typically function as stop codon. The function of HSelP remains unclear, in part due to the inability to express it by gene recombinant technique. This study is to investigate expression and purification of recombinant HSelP in prokaryotic expression system, and its activity to induce apoptosis in vitro.</p><p><b>METHODS</b>The shorter HSelP isoform was cloned. After the selenocysteine (SeCys) at 40th position from N terminus of the HSelP shorter isoform was mutated into cysteine by PCR, it was expressed in E. coli. The expressed product was purified with DEAE column and identified by Western blot. Subsequently, its function on induction of mitochondrial apoptotic activity was studied.</p><p><b>RESULTS</b>The mutant HSelP shorter isoform expressed in prokaryotic system was purified by DEAE column to 90% homogeneity. The purified product, HSelP280m, induced the opening of mitochondrial permeability transition pore (PTP) and decreased the transmembrane potential in a dose-dependent manner. These events could be abolished by PTP specific inhibitors.</p><p><b>CONCLUSION</b>HSelP280m can induce the opening of mitochondrial PTP, which provides a basis for investigating the structure and function of recombinant HSelP.</p>

Cell biological mechanism involved in the effect of sodium selenite on improving insulin sensitivity / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the cell biological mechanism of sodium selenite improving insulin sensitivity in pubertal rats with insulin resistance.</p><p><b>METHODS</b>The content of inositol 1,4,5-trisphosphate (IP3) was examined by anion resin chromatography, and mRNA levels of phosphatidylinositol 3-kinase regulatory subunits (PI3Kp85 alpha) and Se-P were detected by RT-PCR in hepatocyte isolated from pubertal rats with insulin resistance.</p><p><b>RESULTS</b>The mRNA levels of Se-P and PI3Kp85 alpha and content of IP3 in isolated hepatocyte decreased in pubertal male rats with insulin resistance. The above indices increased and reached normal level in rats supplied with selenium. The response to insulin stimulation in isolated hepatocyte in rats with selenium supply was similar to that in the control group, and both groups had higher response than those with high-fat diet. Alone when inhibited by wortmannin, the concentration of IP3 increased slightly in rats with selenium supply, but still was lower than that in the control group.</p><p><b>CONCLUSIONS</b>These results indicate that the effect of selenium improving insulin sensitivity may be related to phosphatidylinositol PI3K signalling pathway. The effect of regulation of IP3 by selenium is not as effective as that by insulin, which may explain the difference of effect between selenium and insulin.</p>