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Braz. j. med. biol. res ; 50(6): e5758, 2017. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-839304


This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , GTP Fosfo-Hidrolases/genética , Falência Hepática Aguda/genética , Proteínas Mitocondriais/genética , Polimorfismo de Nucleotídeo Único , Amônia/sangue , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Hepatite A/genética , Estimativa de Kaplan-Meier , Ácido Láctico/sangue , Falência Hepática Aguda/sangue , Fatores de Risco , Análise de Sobrevida
Braz. j. med. biol. res ; 50(11): e6389, 2017. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-888946


The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.

Humanos , Infecções por Citomegalovirus/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/virologia , Metabolismo dos Lipídeos/fisiologia , Proteínas Mitocondriais/metabolismo , Aterosclerose/metabolismo , Aterosclerose/virologia , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Colesterol/análise , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Hidroximetilglutaril-CoA Redutases/metabolismo , Metabolismo dos Lipídeos/genética , Proteínas Mitocondriais/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/metabolismo , Fatores de Tempo
Oman Medical Journal. 2017; 32 (1): 66-68
em Inglês | IMEMR (Mediterrâneo Oriental) | ID: emr-185728


Mutations in the C19 or f12 gene are known to cause mitochondrial membrane protein associated neurodegeneration [MPAN], which is a neurodegeneration with brain iron accumulation [NBIA] type 4 disorder. To the best of our knowledge, this is the first report of a genetically confirmed case of MPAN from Oman. A novel homozygous deletion of exon 2 of the C19 or f12 gene was confirmed on the proband, a seven-year old girl, who presented with gait instability. Brain magnetic resonance imaging showed iron deposition on the basal ganglia. This report highlights the importance of genetic testing of such a clinically and genetically heterogeneous condition among a population with a high consanguinity rate. To overcome the diagnostic difficulty, implementation of a cost-effective approach to perform cascade screening of carriers at risk is needed as well as programs to address risky consanguineous marriages

Criança , Feminino , Humanos , Encéfalo/patologia , Proteínas Mitocondriais/genética , Consanguinidade , Deleção de Sequência
Ciênc. saúde coletiva ; 20(4): 1099-1107, 04/2015. graf
Artigo em Português | LILACS (Américas) | ID: lil-744885


Trata-se de um estudo sobre o uso do ensino a distância (EaD) como uma estratégia de ensino na educação permanente em saúde (EPS), que teve como objetivo identificar e analisar os limites e possibilidades do uso da EaD na EPS. Estudo de revisão integrativa. O resultado aponta que a EaD é uma estratégia inovadora possível e potencial para a EPS, facilitando o desenvolvimento da aprendizagem dentro ou fora da instituição de saúde, porém é evidente a escassez de pesquisas na área. As limitações para a realização dos programas estão relacionadas à variável tempo, preparação para lidar com as tecnologias e importância do tutor como facilitador da aprendizagem. Conclui-se que o uso da EaD tem tido uma importante contribuição para o desenvolvimento dos recursos humanos em saúde, seja no processo de formação e/ou no processo contínuo de conhecimento.

This is a study on the use of distance learning (EaD, in Portuguese) as a teaching strategy in continuing health education (EPS, in Portuguese), which aimed to identify and analyze the limits and posibilities of using EaD in the EPS. Integrative Review Study. The result shows that EaD is an innovative, possible and potential strategy for EPS, facilitating the development of learning within or outside the health institution, although is evident the lack of research in the area. The limitations for the implementation of the programs are related to the time variable, preparation for dealing with the technologies and the importance of the tutor as a facilitator of learning. It concludes that the use of EaD has an important contribution to the development of human resources in health, is in the process of training and/or in the continuous knowledge process.

Feminino , Humanos , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Grupo com Ancestrais do Continente Africano/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Transformada , Linhagem Celular Tumoral , Proteínas de Transporte de Cátions/genética , Grupos Étnicos , Europa (Continente) , Grupo com Ancestrais do Continente Europeu/genética , Estudo de Associação Genômica Ampla , Projeto HapMap , Proteínas Mitocondriais/genética , Nigéria , Neoplasias Ovarianas/genética , Fenótipo , Análise de Regressão , Proteínas Supressoras de Tumor/genética
J. bras. pneumol ; 41(2): 167-174, Mar-Apr/2015. graf
Artigo em Inglês | LILACS (Américas) | ID: lil-745920


Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic β-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted. .

Objetivo: Investigar o efeito da hipóxia intermitente com um modelo de apneia obstrutiva do sono (AOS) sobre a expressão de uncoupling protein-2 (UCP2), assim como sobre perfis glicêmicos e lipídicos, em camundongos C57BL. Métodos: Camundongos C57BL machos foram expostos a hipóxia intermitente ou hipóxia simulada (grupo controle) 8 h/dia durante 35 dias. A condição de hipóxia intermitente envolveu a exposição dos camundongos a uma atmosfera de 92% de N e 8% de CO2 por 30 s, com redução progressiva de fração de O2 inspirado até 8 ± 1%, seguida por exposição a ar ambiente por 30 s e repetições do ciclo (480 ciclos no período experimental de 8 h). Os pâncreas foram dissecados para isolar as ilhotas. Foi realizada PCR em tempo real utilizando o método TaqMan. Resultados: A expressão do mRNA da UCP2 nas ilhotas pancreáticas foi 20% maior no grupo controle que no grupo hipóxia (p = 0,11). A insulina sérica de jejum foi maior no grupo hipóxia do que no grupo controle (p = 0,01). O modelo de avaliação da homeostase de resistência à insulina indicou que, em comparação com os camundongos controle, aqueles expostos à hipóxia intermitente apresentaram 15% menor resistência à insulina (p = 0,09) e 21% maior função das células beta (p = 0,01). A coloração das ilhotas pancreáticas por imuno-histoquímica não mostrou diferenças significativas entre os grupos em termos da área ou da intensidade das células alfa e beta, marcadas por insulina e glucagon. Conclusões: Segundo nosso conhecimento, esta é a primeira descrição do efeito da hipóxia intermitente sobre a expressão da UCP2. Nossos achados sugerem que UCP2 regula a produção de insulina na AOS. Futuras investigações sobre o papel da UCP2 no controle glicêmico em pacientes com AOS são justificadas. .

Animais , Masculino , Camundongos , Hipóxia/metabolismo , Canais Iônicos/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas Mitocondriais/metabolismo , RNA Mensageiro/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Hipóxia/fisiopatologia , Modelos Animais de Doenças , Resistência à Insulina , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Apneia Obstrutiva do Sono/fisiopatologia
Biomédica (Bogotá) ; 34(4): 546-555, oct.-dic. 2014. tab
Artigo em Inglês | LILACS (Américas) | ID: lil-730938


Introduction : Obesity results from interaction between genetic and environmental risk factors. Objective: To evaluate the effect of three gene variants and environmental factors on obesity and overweight in young people aged 10 to 18 years in a Colombian population. Materials and methods: A total of 424 subjects were selected and separated into three groups for a cross-sectional study; 100 obese and 112 overweight subjects were matched with 212 normal-weight controls. Associations were evaluated between excess weight and three genetic polymorphisms ( UCP3- rs1800849, FTO -rs17817449, and CAPN10 -rs3842570), as well as the family history, the time spent watching television and playing video games, and the diet. Results: A family history of obesity, the time spent watching television and playing video games, the lack of breastfeeding, a low consumption of cereals, legumes, fruits, vegetables, and a high consumption of fast foods were characteristics typically found in obese individuals compared to controls. A significant association between genotype I/I (SNP19 of CAPN10 ) and excess weight was found even with an active lifestyle. In addition, significant associations between the C/C genotype of the UCP3 gene and the G/G and T/T genotypes of the FTO gene and excess weight were found only in young sedentary individuals. Conclusions: In this population, inadequate diet and sedentary lifestyle increased the risk of excess weight. Genotype I/I of SNP19 in CAPN10 was significantly associated with excess weight. In contrast, FTO and UCP3 variants exhibited effects only in sedentary environments.

Introducción. La obesidad resulta de la interacción entre factores de riesgo genéticos y ambientales. Objetivo. Evaluar el efecto de tres variantes genéticas y factores ambientales en el exceso de peso en jóvenes de 10 a 18 años de Medellín, Colombia. Materiales y métodos. Se hizo un estudio transversal en 424 jóvenes divididos en tres grupos: 100 obesos, 112 jóvenes con sobrepeso, y, pareados con ellos, 212 jóvenes con peso adecuado, que conformaron el grupo de control. Se evaluó la asociación entre tres polimorfismos genéticos ( UCP3 -rs1800849, FTO -rs17817449 y CAPN10 -rs3842570) y el exceso de peso, así como su interacción con antecedentes familiares de enfermedad, el tiempo dedicado a ver televisión y a jugar videojuegos y el consumo de alimentos. Resultados. Los antecedentes familiares de obesidad, la dedicación de más de dos horas al día a ver televisión y jugar videojuegos, la falta de lactancia materna, el bajo consumo de cereales, legumbres, frutas y verduras y el gran consumo de comidas rápidas fueron más frecuentes entre los obesos que en los controles. Se observó una asociación significativa entre el genotipo I/I (SNP19 del CAPN10 ) y el exceso de peso, incluso en los jóvenes que llevaban una vida activa. Además, se encontró una asociación significativa entre los genotipos C/C del UCP3 y G/G y T/T del FTO y el exceso de peso, pero solo en los jóvenes sedentarios. Conclusiones. En esta población, la alimentación inadecuada y el sedentarismo aumentaron el riesgo de exceso de peso. El genotipo I/I de SNP19 del CAPN10 se asoció significativamente con el exceso de peso. Algunas variantes del FTO y el UCP3 mostraron tener efecto solo en jóvenes sedentarios.

Adolescente , Criança , Feminino , Humanos , Masculino , Calpaína/genética , Interação Gene-Ambiente , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Antropometria , Adiposidade/genética , Estudos Transversais , Calpaína/fisiologia , Colômbia/epidemiologia , Dieta , Fibras na Dieta , Fast Foods/efeitos adversos , Predisposição Genética para Doença , Genótipo , Canais Iônicos/genética , Atividades de Lazer , Atividade Motora , Proteínas Mitocondriais/genética , Obesidade/epidemiologia , Obesidade/genética , Sobrepeso/epidemiologia , Proteínas/genética , Comportamento Sedentário , Inquéritos e Questionários , Televisão , Jogos de Vídeo
Braz. dent. j ; 25(5): 451-456, Sep-Oct/2014. graf
Artigo em Inglês | LILACS (Américas) | ID: lil-731051


Osteoblastoma is a benign neoplasia and is uncommon in the jaws. In some cases, this lesion presents extremely aggressive local characteristics and is termed aggressive osteoblastoma. Because the clinical, radiographic and histopathologic characteristics are similar to those of a variety of benign and malignant tumors, it poses a diagnostic dilemma. This report presents a case of an aggressive osteoblastoma in the mandible and discusses the differential diagnosis of this lesion. A 13-year-old white male sought the Stomatology Clinic at the State University of Paraíba, Campina Grande, PB, Brazil, complaining of asymptomatic swelling on the left side of his face. Cone-beam computerized tomography showed a multilocular, hypodense bone lesion, located in the body of the left mandible and lower third of the ascending ramus. The initial diagnostic hypothesis was juvenile ossifying fibroma or osteosarcoma. After histopathologic examination, the final diagnosis was aggressive osteoblastoma. Surgical resection with a safety margin was performed. There was no evidence of recurrence after a follow-up period of 4 years.

O osteoblastoma é uma neoplasia benigna e incomum nos maxilares. Em alguns casos esta lesão apresenta características locais extremamente agressivas, sendo denominada osteoblastoma agressivo. Devido às características clínicas, radiográficas e histopatológicas serem similares a uma variedade de tumores benignos e malignos, o seu diagnóstico é um dilema. Este relato apresenta o caso de um osteoblastoma agressivo na mandíbula e discute o diagnóstico diferencial desta lesão. Paciente, branco, 13 anos de idade, foi atendido na Clínica de Estomatologia da Universidade Estadual da Paraíba, Campina Grande, PB, Brasil, queixando-se de aumento de volume assintomático do lado esquerdo de sua face. A tomografia computadorizada de feixe cônico revelou uma lesão óssea hipodensa multilocular, localizada no corpo do lado esquerdo da mandíbula e no terço inferior do ramo ascendente da mandíbula. A hipótese diagnóstica foi de fibroma ossificante juvenil e osteosarcoma. Após exame histopatológico, o diagnóstico final foi osteoblastoma agressivo. Foi realizada ressecção cirúrgica com margem de segurança. Não houve sinais de recorrência após 4 anos de acompanhamento.

Animais , Humanos , Camundongos , Apoptose/fisiologia , Proteínas de Transporte/metabolismo , Proteínas Mitocondriais/metabolismo , Anticorpos/metabolismo , Anticorpos/farmacologia , /metabolismo , Linfócitos B/fisiologia , Caspase 9 , Células Cultivadas , Proteínas de Transporte/genética , Caspases/metabolismo , Ativação Enzimática , Embrião de Mamíferos/fisiologia , Marcação de Genes , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Knockout , Proteínas Mitocondriais/genética , Taxa de Sobrevida , Células-Tronco/citologia , Células-Tronco/metabolismo , Linfócitos T/fisiologia
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-37644


Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.

Regiões 3' não Traduzidas , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Potencial da Membrana Mitocondrial , Proteínas de Membrana/genética , MicroRNAs/metabolismo , Mitocôndrias/genética , Dinâmica Mitocondrial , Proteínas Mitocondriais/genética , Biossíntese de Proteínas , RNA Mensageiro/genética
Arq. bras. endocrinol. metab ; 57(8): 603-611, Nov. 2013. tab
Artigo em Inglês | LILACS (Américas) | ID: lil-696899


OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS: SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS: LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS: Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.

OBJETIVO: Avaliar a associação de polimorfismos de nucleotídeo único (SNPs) em cinco genes: leptina, receptor da leptina (LEPR), adiponectina (APM1), receptor ativado por proliferadores de peroxissomas gama (PPARG) e proteína desacopladora 1 com parâmetros antropométricos, metabólicos e dietéticos em uma coorte sul-brasileira composta por 325 crianças acompanhadas desde o nascimento até os 4 anos. MATERIAIS E MÉTODOS: Os SNPs foram analisados por meio da reação em cadeia da polimerase e sua associação com os fenótipos foi avaliada utilizando teste T, análise de variância e análise fatorial. RESULTADOS: O alelo LEPR223Arg (rs1137101) foi associado a uma maior ingestão energética diária aos 4 anos (P = 0,002; Pcorrigido = 0,024). Os portadores do alelo PPARG12Ala (rs1801282) apresentaram maior glicemia em relação aos homozigotos Pro/Pro (P = 0,007; Pcorrigido = 0,042). CONCLUSÕES: Dois dos seis SNPs estudados apresentaram associações consistentes, mostrando que aos 4 anos de idade já é possível detectar as influências de variantes genéticas sobre a suscetibilidade ao excesso de peso.

Pré-Escolar , Humanos , Lactente , Recém-Nascido , Adiponectina/genética , Ingestão de Energia , Canais Iônicos/genética , Leptina/genética , Proteínas Mitocondriais/genética , PPAR gama/genética , Receptores para Leptina/genética , Pesos e Medidas Corporais , Brasil , Glicemia/análise , Colesterol/sangue , Comportamento Alimentar , Modelos Lineares , Obesidade/genética , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
Yonsei Medical Journal ; : 603-608, 2013.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-193945


PURPOSE: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. MATERIALS AND METHODS: 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5'-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. RESULTS: When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, pG variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, pG variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.

China , Feminino , GTP Fosfo-Hidrolases/genética , Regulação da Expressão Gênica , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão/genética , Modelos Logísticos , Masculino , Proteínas Mitocondriais/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-14631


Diphyllobothrium nihonkaiense has been reported in Korea as Diphyllobothrium latum because of their close morphologic resemblance. We have identified a human case of D. nihonkaiense infection using the mitochondrial cytochrome c oxidase subunit I (cox1) gene sequence analysis. On 18 February 2012, a patient who had consumed raw fish a month earlier visited our outpatient clinic with a long tapeworm parasite excreted in the feces. The body of the segmented worm was 2 m long and divided into the scolex (head) and proglottids. It was morphologically close to D. nihonkaiense and D. latum. The cox1 gene analysis showed 99.4% (340/342 bp) homology with D. nihonkaiense but only 91.8% (314/342 bp) homology with D. latum. The present study suggested that the Diphyllobothrium spp. infection in Korea should be analyzed with specific DNA sequence for an accurate species identification.

Animais , Ciclo-Oxigenase 1/genética , Difilobotríase/parasitologia , Diphyllobothrium/enzimologia , Feminino , Proteínas de Helminto/genética , Humanos , Proteínas Mitocondriais/genética
Arq. bras. endocrinol. metab ; 56(4): 215-225, June 2012. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: lil-640695


It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) e obesidade e que indivíduos suscetíveis geneticamente podem desenvolver essas doenças metabólicas após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2 e/ou à obesidade. A proteína desacopladora 1 (UCP1) é principalmente expressa no tecido adiposo marrom e atua na termogênese, regulação do gasto energético e proteção contra o estresse oxidativo, mecanismos associados tanto à patogênese do DM2 como à obesidade. Portanto, UCP1 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos relataram que os polimorfismos -3826A/G, -1766A/G e -112A/C na região promotora, Ala64Thr no éxon 2 e Met299Leu no éxon 5 do gene UCP1 estão possivelmente associados à obesidade e/ou ao DM2. Entretanto, os resultados são ainda controversos em diferentes populações. Então, o objetivo deste estudo foi revisar o papel da UCP1 no desenvolvimento dessas doenças metabólicas.

Humanos , /genética , Canais Iônicos/fisiologia , Proteínas Mitocondriais/fisiologia , Obesidade/genética , Predisposição Genética para Doença , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Polimorfismo Genético
Arq. bras. endocrinol. metab ; 55(4): 239-248, June 2011. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: lil-593115


It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.

Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) bem como de suas complicações crônicas e que indivíduos geneticamente suscetíveis podem desenvolver essa doença após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2. A proteína desacopladora 2 (UCP2) é expressa em diversos tecidos e atua na proteção contra o estresse oxidativo, na regulação negativa da secreção de insulina pelas células-beta e no metabolismo dos ácidos graxos, mecanismos associados tanto à patogênese do DM2 como a suas complicações crônicas. Portanto, o gene UCP2 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos têm relatado que três polimorfismos comuns no gene UCP2 estão possivelmente associados ao DM2 e/ou à obesidade. Apenas poucos estudos investigaram esses polimorfismos em relação às complicações crônicas do diabetes, obtendo resultados pouco conclusivos.

Humanos , /genética , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Polimorfismo Genético , /complicações , Doenças Mitocondriais/metabolismo
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-151032


Diphyllobothrium nihonkaiense was first described by Yamane in 1986 but the taxonomical features have been obscure due to lack of critical morphologic criteria in its larval and adult stages. In Korea, this tapeworm had long been known as Diphyllobothrium latum. In this study, we observed 62 specimens collected from Korean residents and analyzed them by morphological features and nucleotide sequences of mitochondrial cox1 gene as well as the ITS1 region. Adult tapeworms were examined after carmine or trichrome stain. Longitudinal sections of the gravid proglottids showed an obtuse angle of about 150 degree between the cirrus sac and seminal vesicle. This angle is known as a major differential point compared with that of D. latum. Nucleotide sequence differences between D. latum and the specimens from Koreans represented 17.3% in mitochondrial DNA cox1 gene. Sequence divergence of ITS1 among 4 Korean isolates was 0.3% and similarity was 99.7% with D. nihonkaiense and D. klebanovskii. All of the Korean specimens analyzed in this study were identified as being D. nihonkaiense (n = 62). We propose its Korean name as "Dong-hae-gin-chon-chung" which means 'long tapeworm of the East Sea' for this newly analyzed diphyllobothriid tapeworm in Korea.

Adulto , Idoso , Estruturas Animais/anatomia & histologia , Animais , Análise por Conglomerados , Ciclo-Oxigenase 1/genética , DNA de Helmintos/química , DNA Intergênico/química , DNA Ribossômico/química , Difilobotríase/parasitologia , Diphyllobothrium/anatomia & histologia , Feminino , Proteínas de Helminto/genética , Humanos , Coreia (Geográfico) , Masculino , Microscopia , Microscopia Eletrônica de Varredura , Proteínas Mitocondriais/genética , Filogenia , Análise de Sequência de DNA , Homologia de Sequência
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-634645


In order to evaluate the effect of mitofusin-2 gene (mfn2) on proliferation and chemotherapy sensitivity of human breast carcinoma cell line MCF-7 in vitro, pEGFPmfn2 plasmid carrying full length of mitofusin-2 gene was transfected, by using sofast, into MCF-7 cells. Mitofusin-2 gene expression in MCF-7 cells transfected by sofast after 48 h was detected by PCR and Western blotting, and the stable expression of GFP protein in MCF-7 cells by Western blot analysis. The proliferation of MCF-7 cells was assayed by MTT and cell counting. By using PI method, the effects of mfn2 on the cell cycle distribution of MCF-7 were measured. Annexin-V/PI double labeling method was employed to detect the changes in apoptosis induced by chemotherapeutics before and after transfection. The results showed that the MCF-7 cells transfected with mfn2 gene could stably and highly express GFP protein. MTT assay revealed that after transfection of mfn2 cDNA, the proliferation of MCF-7 cells was significantly inhibited. DNA histogram showed that cells arrested in S phase, and the percentage of S phase cells was 42.7, 17.2 and 19.6 in mfn2 cDNA transfection group, blank plasmid transfection group and blank control group, respectively (P<0.05). The apoptosis ratio of the cells transfected with mfn2 gene was increased from 3.56% to 15.95%, that of the cells treated with camptothecin (CAMP) followed by mfn2 gene transfection was 69.6%, and that in blank plasmid transfection group and blank control group was 31.0% and 23.4% respectively (P<0.05). It was suggested that transfection of mfn2 gene could significantly inhibit the proliferation of MCF-7 cells and promote their sensitivity to CAMP with a synergic effect.

Antineoplásicos Fitogênicos/farmacologia , Apoptose , Camptotecina/farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Transfecção
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-37043


Recent studies have provided some clues with regard to the relationship existing between uncoupling protein 1 (UCP1) and blood pressure in animal experiments. In an attempt to determine the genetic polymorphisms that are associated with blood pressure in humans, we have analyzed genetic polymorphisms in UCP1 gene. In this study, we assessed the association between UCP1 genotypes and systolic blood pressure (SBP) and diastolic blood pressure (DBP), in a population comprised of 832 Korean female subjects, using a general linear model, which was adjusted for age and body mass index (BMI). Among 4 genetic polymorphisms and the haplotypes constructed from them, haplotype3 of UCP1, UCP1-ht3[GAGA], evidenced significant associations with SBP (p=0.005) and DBP (p=0.013). However, this haplotype was not significantly associated with obesity phenotypes, including BMI or fat mass (p>0.05), thereby suggesting that its association with blood pressure was independent of obesity phenotypes.

Adulto , Alelos , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Genótipo , Haplótipos , Humanos , Canais Iônicos/genética , Coreia (Geográfico) , Proteínas Mitocondriais/genética , Modelos Genéticos , Obesidade/genética , Fenótipo , Polimorfismo Genético
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-205420


Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.

Adulto , Grupo com Ancestrais do Continente Asiático , Análise Mutacional de DNA , DNA Mitocondrial/análise , Complexo I de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Humanos , Coreia (Geográfico) , Síndrome MELAS/genética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Mutação de Sentido Incorreto , Linhagem , Polimorfismo Genético
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-92080


Citrin is a liver-type mitochondrial aspartate-glutamate carrier encoded by the SLC25A13 gene, and its deficiency causes adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Here, the authors investigated clinical findings in Korean infants with NICCD and performed mutation analysis on the SLC25A13 gene. Of 47 patients with neonatal cholestasis, three infants had multiple aminoacidemia (involving citrulline, methionine, and arginine) and galactosemia, and thus were diagnosed as having NICCD. Two of these three showed failure to thrive. The laboratory findings showed hypoproteinemia and hyperammonemia, and liver biopsies revealed micro-macrovesicular fatty liver and cholestasis. The three patients each harbored compound heterozygous 1,638-1,660 dup/ S225X mutation, compound heterozygous 851del4/S225X mutation, and heterozygous 1,638-1,660 dup mutation, respectively. With nutritional manipulation, liver functions were normalized and catch-up growth was achieved. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Korean infants.

Aminoácidos/sangue , Proteínas de Ligação ao Cálcio/deficiência , Colestase Intra-Hepática/etiologia , Citrulinemia/genética , Humanos , Lactente , Proteínas de Membrana Transportadoras/genética , Proteínas Mitocondriais/genética , Mutação , Transportadores de Ânions Orgânicos/deficiência
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-201415


Leptin receptor deficiency causes morbid obesity and hyperlipidemia in mice. Since physical exercise enhances energy expenditure, it is an important part of successful weight-control regimens. We investigated the mechanism by which swim training regulates leptin receptor deficiency-induced obesity and lipid disorder in a mouse model of obesity (obese db/db mouse). Swim training for 6 weeks significantly decreased body weight gain and adipose tissue mass in both sexes of obese and lean mice, compared to their respective sedentary controls. These effects were particularly evident in obese mice. Swim training also caused significant decreases in serum levels of triglycerides, free fatty acids and total cholesterol in both obese and lean mice. In obese mice, swim training increased the levels of mRNAs and proteins encoding uncoupling protein 1 (UCP1), UCP2 and UCP3 in brown adipose tissue, white adipose tissue and skeletal muscle, respectively. In conclusion, these findings suggest that, in mice, swim training can effectively prevent body weight gain, adiposity and lipid disorders caused by leptin receptor deficiency, in part through activation of UCPs in adipose tissue and skeletal muscle, which may contribute to alleviating metabolic syndromes, such as obesity, hyperlipidemia and type 2 diabetes.

Tecido Adiposo/metabolismo , Animais , Peso Corporal , Feminino , Canais Iônicos/genética , Metabolismo dos Lipídeos , Masculino , Camundongos , Proteínas Mitocondriais/genética , Músculo Esquelético/metabolismo , Obesidade/genética , Condicionamento Físico Animal , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/deficiência , Receptores para Leptina , Natação
Rev. invest. clín ; 58(4): 289-295, jul.-ago. 2006. ilus, tab
Artigo em Espanhol | LILACS (Américas) | ID: lil-632376


Variegate porphyria (VP) results from a hereditary deficiency of protoporphyrinogen oxidase (PPOX) that is transmitted in an autosomal dominan fashion. The diagnosis is based on the clinical symptoms and is confirmed biochemically. Sometimes, however, these diagnostic tools reveal limitations in establishing the definitive diagnosis of the prevailing type of acute porphyria. In these patients, molecular genetic analyses can be useful. We performed molecular genetic studies in 13 Chilean families by PCR amplification of the PPOX gene, conformation sensitive gel electrophoresis, and automated DNA sequencing. In five symptomatic patients from different families, respectively, the biochemical data confirmed the diagnosis of VP. In seven other families, however, the biochemical studies were not conclusive. Furthermore, the original biochemical analysis in one clinically severely affected patient from a further family even suggested the diagnosis of erythropoietic protoporphyria (EPP). Beside the respective index patients, we studied 78 asymptomatic family members and 50 healthy, unrelated individuals for control purposes. In five families, the previous diagnosis of VP could be confirmed genetically. Further, half of the asymptomatic relatives revealed a mutation in the PPOX gene, consisting of three missense mutations and two deletion mutations. Mutation R168H that had been already described previously in German VP families was found in a Chilean family of German origin. Further, two novel missense mutations, designated L74P and G232S, could be detected. In four Chilean families, we found the deletion 1330deICT that had also been previously described in three Swedish VP families. The second deletion, 1239delTACAC, has not been described anywhere else but Chile and could be identified in seven families. One patient who was initially diagnosed with EPP turned out to be a compound heterozygote for mutations on both alíeles of the PPOX gene. In conclusion, our molecular genetic analyses unequivocally confirmed the diagnosis of VP in seven families who originally had revealed inconclusive biochemical data. Further, early genetic analysis allows for the identification of asymptomatic mutation carriers, thereby offering the possibility of adequate counselling and the prevention of potentially life-threatening acute porphyric attacks.

La porfiria variegata (PV), enfermedad de origen genético con forma de herencia autosómica dominante, se debe a deficiencia en la actividad protoporfirinógeno oxidasa (PPOX). Su diagnóstico se basa en antecedentes clínicos y se confirma con análisis bioquímicos. Éstos, en algunos casos, pueden presentar limitaciones para establecer el diagnóstico definitivo de la variedad de porfiria aguda, situación en que el estudio genético molecular puede resultar útil. Se efectuó estudio genético en trece familias chilenas usando amplificación del gen PPOX por PCR, electroforesis conformacional y secuenciación automática de DNA. Cinco de estas familias incluían pacientes índices sintomáticos con diagnóstico bioquímico establecido de PV; otras siete familias incluían pacientes índices con estudio bioquímico no concluyente de la variedad de porfiria aguda y, finalmente, una familia con diagnóstico previo de protoporfiria eritropoyética (PPE). Además, se estudiaron 78 familiares asintomáticos y 50 personas sanas, no relacionadas, como controles. En cinco familias el estudio genético confirmó el diagnóstico bioquímico previo de PV. El 50% de los familiares asintomáticos resultaron ser portadores de una mutación en el gen PPOX. Se identificaron tres mutaciones por sustitución de bases: la R168H, descrita en familias de origen alemán y dos nuevas mutaciones, designadas L74P y G232S. También se identificaron dos mutaciones por deleción de bases designadas 1330delCT y la 1239delTACAC. La primera, que había sido descrita previamente en tres familias suecas, se encontró en cuatro familias chilenas. La segunda se encontró en siete familias y no ha sido descrita previamente. El estudio genético permitió mostrar que un paciente que originalmente fue diagnosticado con PPE correspondía a un heterocigoto compuesto para dos mutaciones en el gen PPOX. En conclusión, los estudios moleculares permitieron confirmar el diagnóstico de PV en cinco familias, efectuar diagnóstico de PV en familias en las cuales los datos bioquímicos no eran concluyentes, corregir el diagnóstico original en una familia e identificar portadores asintomáticos entre los familiares de los pacientes índices. Los estudios genéticos moleculares ayudan a realizar un adecuado consejo genético a pacientes y familiares y hace posible practicar prevención de las crisis agudas de porfiria, las que son potencialmente mortales.

Humanos , Porfiria Variegada/genética , Protoporfirinogênio Oxidase/genética , Chile , Flavoproteínas/genética , Predisposição Genética para Doença , Mutação , Proteínas Mitocondriais/genética , Porfiria Variegada/diagnóstico , Porfiria Variegada/enzimologia