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Asian Journal of Andrology ; (6): 238-242, 2022.
Article in English | WPRIM | ID: wpr-928542


Cilium, an organelle with a unique proteome and organization, protruding from the cell surface, generally serves as a force generator and signaling compartment. During ciliogenesis, ciliary proteins are synthesized in cytoplasm and transported into cilia by intraflagellar transport (IFT) particles, where the inner counterparts undergo reverse trafficking. The homeostasis of IFT plays a key role in cilial structure assembly and signaling transduction. Much progress has been made on the mechanisms and functions of IFT; however, recent studies have revealed the involvement of IFT particle subunits in organogenesis and spermatogenesis. In this review, we discuss new concepts concerning the molecular functions of IFT protein IFT25 and how its interactions with other IFT particle subunits are involved in mammalian development and fertility.

Animals , Biological Transport , Carrier Proteins/metabolism , Cilia/metabolism , Flagella/metabolism , Male , Mammals/metabolism , Organogenesis , Proteins/metabolism , Signal Transduction
Acta Physiologica Sinica ; (6): 301-308, 2022.
Article in Chinese | WPRIM | ID: wpr-927606


Nogo-B receptor (NgBR) is a specific receptor of Nogo-B, a member of reticulon 4 protein family. It is widely expressed in many tissues and mainly located in cell membrane and endoplasmic reticulum. Previous studies have revealed that NgBR is involved in a variety of physiological and pathophysiological processes, such as dolichol synthesis, lipid metabolism, cholesterol trafficking, insulin resistance, vascular remodeling and angiogenesis, tumorigenesis and nervous system diseases. Further studies on the molecular characteristics and biological function of NgBR might be of great significance to understand its role in diverse diseases and provide possible clinical strategies for the treatment of diseases.

Carrier Proteins/metabolism , Endoplasmic Reticulum/metabolism , Lipid Metabolism , Nogo Proteins/metabolism , Receptors, Cell Surface/metabolism
Acta cir. bras ; 32(6): 429-439, June 2017. graf
Article in English | LILACS | ID: biblio-886202


Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

Animals , Male , Rats , Reperfusion Injury/drug therapy , Protective Agents/therapeutic use , Dexmedetomidine/therapeutic use , Diabetes Mellitus, Experimental/complications , Kidney/drug effects , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Signal Transduction/drug effects , Carrier Proteins/drug effects , Carrier Proteins/metabolism , Rats, Sprague-Dawley , Streptozocin , p38 Mitogen-Activated Protein Kinases/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Kidney/injuries , Kidney/pathology
Int. arch. otorhinolaryngol. (Impr.) ; 19(2): 161-165, Apr-Jun/2015. tab
Article in English | LILACS | ID: lil-747147


Introduction Literature data are not conclusive as to the influence of neonatal complications in the maturational process of the auditory system observed by auditory brainstem response (ABR) in infants at term and preterm. Objectives Check the real influence of the neonatal complications in infants by the sequential auditory evaluation. Methods Historical cohort study in a tertiary referral center. A total of 114 neonates met inclusion criteria: treatment at the Universal Neonatal Hearing Screening Program of the local hospital; at least one risk indicator for hearing loss; presence in both evaluations (the first one after hospital discharge from the neonatal unit and the second one at 6 months old); all latencies in ABR and transient otoacoustic emissions present in both ears. Results The complications that most influenced the ABR findings were Apgar scores less than 6 at 5 minutes, gestational age, intensive care unit stay, peri-intraventricular hemorrhage, and mechanical ventilation. Conclusion Sequential auditory evaluation is necessary in premature and term newborns with risk indicators for hearing loss to correctly identify injuries in the auditory pathway. .

Animals , Humans , Mice , Carcinoma in Situ/metabolism , Carcinoma, Pancreatic Ductal/metabolism , Carrier Proteins/metabolism , Microfilament Proteins/metabolism , Pancreatic Neoplasms/metabolism , Transcription Factors/metabolism , Cell Line, Tumor , Carcinoma in Situ/genetics , Carcinoma in Situ/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/secondary , Carrier Proteins/genetics , Disease Models, Animal , Disease Progression , Epithelial-Mesenchymal Transition , Mice, Knockout , Microfilament Proteins/deficiency , Microfilament Proteins/genetics , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pseudopodia/metabolism , RNA Interference , Survival Analysis , Time Factors , Transfection , Transcription Factors/genetics
Radiol. bras ; 48(2): 93-100, Mar-Apr/2015. graf
Article in English | LILACS | ID: lil-746612


Objective: To present a detailed explanation on the processing of magnetic susceptibility weighted imaging (SWI), demonstrating the effects of echo time and sensitive mask on the differentiation between calcification and hemosiderin. Materials and Methods: Computed tomography and magnetic resonance (magnitude and phase) images of six patients (age range 41– 54 years; four men) were retrospectively selected. The SWI images processing was performed using the Matlab’s own routine. Results: Four out of the six patients showed calcifications at computed tomography images and their SWI images demonstrated hyperintense signal at the calcification regions. The other patients did not show any calcifications at computed tomography, and SWI revealed the presence of hemosiderin deposits with hypointense signal. Conclusion: The selection of echo time and of the mask may change all the information on SWI images, and compromise the diagnostic reliability. Amongst the possible masks, the authors highlight that the sigmoid mask allows for contrasting calcifications and hemosiderin on a single SWI image. .

Objetivo: Expor em detalhes o processamento da imagem ponderada em suscetibilidade magnética (susceptibility weighted imaging – SWI), destacando o efeito da escolha do tempo de eco e da máscara sensível à diferenciação de calcificação e hemossiderina simultaneamente. Materiais e Métodos: Imagens de tomografia computadorizada e por ressonância magnética (magnitude e fase) foram selecionadas, retrospectivamente, de seis pacientes (idades entre 41 e 54 anos; quatro homens). O processamento das imagens SWI foi realizado em rotina própria no programa Matlab. Resultados: Dos seis pacientes estudados, quatro apresentaram calcificações nas imagens de tomografia computadorizada. Nestes, as imagens SWI mostraram sinal hiperintenso para as regiões de calcificações. Os outros dois pacientes não apresentaram calcificações nas imagens de tomografia computadorizada e apresentaram depósito de hemossiderina com sinal hipointenso na imagem SWI. Conclusão: A escolha do tempo de eco e da máscara pode alterar toda a informação da imagem SWI e comprometer a confiabilidade diagnóstica. Dentre as possíveis máscaras, destacamos que a máscara sigmoide permite contrastar calcificação e hemossiderina em uma única imagem SWI. .

Animals , Mice , Alternative Splicing/genetics , Carrier Proteins/genetics , Carrier Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Polypyrimidine Tract-Binding Protein/genetics , Tropomyosin/genetics , Base Sequence , Binding Sites , DNA Primers , Exons , Genetic Vectors , Ligands , Open Reading Frames , Polymerase Chain Reaction , Polypyrimidine Tract-Binding Protein/metabolism , Recombinant Proteins/metabolism , Repressor Proteins/metabolism , Transfection
Rev. bras. ginecol. obstet ; 37(1): 30-35, 01/2015. tab
Article in Portuguese | LILACS | ID: lil-732873


OBJETIVO: Avaliar a prevalência da baixa densidade mineral óssea (DMO) em mulheres na pós-menopausa tratadas de câncer de mama. MÉTODOS: Estudo de corte transversal que incluiu 115 mulheres tratadas de câncer de mama atendidas em Hospital Universitário do Sudeste do Brasil. Foram incluídas mulheres com amenorreia há 12 meses ou mais e 45 anos ou mais de idade, tratadas de câncer de mama e livres de doença há pelo menos 5 anos. A DMO foi mensurada pelos raios-X de dupla energia em coluna lombar (L1 a L4) e colo de fêmur. Considerou-se baixa DMO quando valores de T-score de coluna total e/ou colo de fêmur <-1,0 Score de Delphi (DP) (osteopenia e osteoporose). Por meio de entrevista, foram avaliados fatores de risco para baixa DMO. Na análise estatística, empregaram-se os testes do χ2 ou Exato de Fisher. RESULTADOS: A média de idade das pacientes foi 61,6±10,1 anos e o tempo de menopausa, 14,2±5,6 anos, com tempo médio de seguimento de 10,1±3,9 anos. Considerando coluna e colo de fêmur, 60% das mulheres tratadas de câncer de mama apresentavam baixa DMO. Avaliando os fatores de risco para baixa DMO, foi encontrada diferença significativa na distribuição percentual quanto à idade (maior porcentagem de mulheres com mais de 50 anos e baixa DMO), história pessoal de fratura prévia (11,6% com baixa DMO e nenhuma com DMO normal) e índice de massa corpórea. Maior frequência de obesidade foi observada entre mulheres com DMO normal (63%) quando comparadas àquelas com baixa DMO (26,1%; p<0,05). CONCLUSÃO: Mulheres na pós-menopausa tratadas de câncer de mama apresentaram elevada prevalência de baixa DMO (osteopenia e/ou osteoporose). .

PURPOSE: To evaluate the prevalence of low bone mineral density (BMD) in postmenopausal breast cancer survivors. METHODS: In this cross-sectional study, 115 breast cancer survivors, seeking healthcare at a University Hospital in Brazil, were evaluated. Eligibility criteria included women with amenorrhea ≥12 months and age ≥45 years, treated for breast cancer and metastasis-free for at least five years. BMD was measured by DEXA at the lumbar spine (L1-L4) and femoral neck. Low BMD was considered when total-spine and/or femoral-neck T-score values were <-1.0 Delphi Score (DP) (osteopenia and osteoporosis). The risk factors for low BMD were assessed by interview. Data were analyzed statistically by the χ2 test and Fisher's exact test. RESULTS: The mean age of breast cancer survivors was 61.6±10.1 years and time since menopause was 14.2±5.6 years, with a mean follow-up of 10.1±3.9 years. Considering spine and femoral neck, 60% of breast cancer survivors had low BMD. By evaluating the risk factors for low BMD, a significant difference was found in the percent distribution for age (higher % of women >50 years with low BMD), personal history of previous fracture (11.6% with low BMD versus 0% with normal BMD) and BMI. A higher frequency of obesity was observed among women with normal BMD (63%) compared to those with low BMD (26.1%) (p<0.05). CONCLUSION: Postmenopausal breast cancer survivors had a high prevalence of osteopenia and osteoporosis. .

Animals , Rats , Bile Acids and Salts/metabolism , Bile Canaliculi/metabolism , Carrier Proteins/metabolism , Hydroxysteroid Dehydrogenases , Membrane Glycoproteins , Adenosine Triphosphatases/metabolism , Biological Transport , COS Cells , Carcinoembryonic Antigen/biosynthesis , Carrier Proteins/biosynthesis , DNA Primers , DNA, Complementary , Ileum/metabolism , Kinetics , Mutagenesis, Site-Directed , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/metabolism , Transfection , Taurocholic Acid/metabolism
Rev. saúde pública ; 49: 1-9, 27/02/2015. tab, graf
Article in English | LILACS | ID: lil-742296


OBJECTIVE To validate a screening instrument using self-reported assessment of frailty syndrome in older adults. METHODS This cross-sectional study used data from the Saúde, Bem-estar e Envelhecimento study conducted in Sao Paulo, SP, Southeastern Brazil. The sample consisted of 433 older adult individuals (≥ 75 years) assessed in 2009. The self-reported instrument can be applied to older adults or their proxy respondents and consists of dichotomous questions directly related to each component of the frailty phenotype, which is considered the gold standard model: unintentional weight loss, fatigue, low physical activity, decreased physical strength, and decreased walking speed. The same classification proposed in the phenotype was utilized: not frail (no component identified); pre-frail (presence of one or two components), and frail (presence of three or more components). Because this is a screening instrument, “process of frailty” was included as a category (pre-frail and frail). Cronbach’s α was used in psychometric analysis to evaluate the reliability and validity of the criterion, the sensitivity, the specificity, as well as positive and negative predictive values. Factor analysis was used to assess the suitability of the proposed number of components. RESULTS Decreased walking speed and decreased physical strength showed good internal consistency (α = 0.77 and 0.72, respectively); however, low physical activity was less satisfactory (α = 0.63). The sensitivity and specificity for identifying pre-frail individuals were 89.7% and 24.3%, respectively, while those for identifying frail individuals were 63.2% and 71.6%, respectively. In addition, 89.7% of the individuals from both the evaluations were identified in the “process of frailty” category. CONCLUSIONS The self-reported assessment of frailty can identify the syndrome among older adults and can be used as a screening tool. Its ...

OBJETIVO Validar instrumento de rastreamento por avaliação autorreferida da síndrome de fragilidade entre idosos. MÉTODOS Estudo transversal com dados do estudo Saúde, Bem-estar e Envelhecimento, realizado em São Paulo, SP. A amostra probabilística foi constituída por 433 idosos (idade ≥ 75 anos) avaliados em 2009. O instrumento autorreferido utilizado pode ser aplicado a idosos ou proxi-informantes e foi composto por questões dicotômicas relacionadas diretamente a cada componente do fenótipo de fragilidade considerado padrão-ouro: perda de peso não intencional, fadiga, baixa atividade física, redução de força e de velocidade de marcha. Manteve-se a classificação proposta no fenótipo: não frágil (nenhum componente identificado); pré-frágil (presença de um ou dois componentes) e frágil (presença de três ou mais componentes). Por tratar-se de instrumento de rastreamento, incluiu-se a categoria processo de fragilização (pré-frágil e frágil). Utilizou-se o coeficiente α de Cronbach na análise psicométrica para avaliar confiabilidade e validade de critério, sensibilidade, especificidade e valores preditivos positivo e negativo. Para verificar a adequação do número de componentes propostos, utilizou-se a análise fatorial. RESULTADOS Os componentes “redução de velocidade de caminhada” e “redução de força” apresentaram boa consistência interna (α = 0,77 e α = 0,72, respectivamente) e a “baixa atividade física” (α = 0,63) foi um pouco menos satisfatória. A sensibilidade e a especificidade para identificação dos pré-frágeis foram de 89,7% e 24,3% e dos frágeis, 63,2% e 71,6%, respectivamente. A categoria “processo de fragilização” identificou, igualmente, 89,7% das pessoas em ambas as avaliações. CONCLUSÕES O instrumento de avaliação de fragilidade autorreferida é capaz de identificar a síndrome entre as pessoas idosas, podendo ser utilizado como instrumento de rastreamento, ...

Animals , Humans , ADAM Proteins/metabolism , Carrier Proteins/metabolism , Hemarthrosis/etiology , Hemarthrosis/metabolism , Hemophilia A/complications , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Synovitis/etiology , Synovitis/metabolism
Hist. ciênc. saúde-Manguinhos ; 21(4): 1113-1129, Oct-Dec/2014.
Article in Portuguese | LILACS | ID: lil-732519


Neste artigo examino como geneticistas contemporâneos que pesquisam a história e a configuração da população brasileira interagem com outras disciplinas. Para tanto, tomei como estudo de caso artigos publicados por geneticistas que investigam a presença de variantes da hemoglobina S no Brasil, os quais pretendem claramente contribuir para a análise de questões como escravidão ou identidade étnica no país. Contrastando esses estudos com trabalhos contemporâneos da história e das ciências sociais, problematizo a centralidade explanatória da “origem” nos estudos genéticos analisados, bem como a falta de interação com questões epistemológicas de outras áreas do saber.

In this article I examine how contemporary geneticists investigating the history and configuration of the Brazilian population engage with other academic disciplines. To do so I use as a case study some articles published by geneticists researching the presence of hemoglobin S variants in Brazil, in which there is a clear pretension to contribute to the analysis of issues such as slavery or Brazil’s ethnic identity. By contrasting these studies with contemporary works from history and the social science, the explanatory centrality of “origin” in the genetic studies analyzed is problematized, as is the lack of interaction with the epistemological characteristics of other areas of knowledge.

Animals , Rats , Hemoglobins/metabolism , Iron-Binding Proteins , Iron/metabolism , Reticulocytes/metabolism , Biological Transport , Carrier Proteins/metabolism , Ferric Compounds/metabolism , Integrins/metabolism , Rats, Wistar , Transferrin/metabolism
Mem. Inst. Oswaldo Cruz ; 109(7): 960-963, 11/2014. tab
Article in English | LILACS | ID: lil-728799


Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

Adult , Female , Humans , Male , Middle Aged , Carrier Proteins/genetics , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/genetics , Polymorphism, Single Nucleotide/genetics , Brazil , Carrier Proteins/metabolism , Genetic Predisposition to Disease , HTLV-I Infections/genetics , Inflammasomes/immunology , Interleukin-1/metabolism , Protective Factors
Arq. bras. endocrinol. metab ; 58(8): 869-872, 11/2014. tab, graf
Article in English | LILACS | ID: lil-729783


Metastatic tumors to the pituitary gland are an unusual complication typically seen in elderly patients with diffuse malignant disease. Breast and lung are the commonest sites of the primary tumor. Prognosis of patients with breast cancer metastasis is poor and depends on the primary neoplastic extension. We report a 54 year-old woman with breast cancer metastasis to the pituitary stalk first diagnosed because of visual disturbance with no other symptoms. Pituitary gland stalk metastasis is a very uncommon find and this case report includes a literature review.

Os tumores hipofisários malignos são raros e geralmente se constituem de metástases de neoplasias disseminadas. Câncer de mama e pulmão são os sítios primários mais frequentes e o prognóstico depende do grau de comprometimento da doença. Este é o relato do caso de uma mulher de 54 anos que apresentou uma lesão tumoral restrita à haste hipofisária, que se revelou como metástase do câncer de mama previamente conhecido. O acometimento da haste hipofisária é muito raro, motivo pelo qual descrevemos o caso com a revisão da literatura específica.

Female , Humans , Middle Aged , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Pituitary Neoplasms/secondary , Adrenocorticotropic Hormone/analysis , Carcinoma, Ductal, Breast/diagnosis , Carrier Proteins/metabolism , Glycoproteins/metabolism , Magnetic Resonance Imaging , Pituitary Neoplasms/diagnosis
Braz. dent. j ; 25(5): 451-456, Sep-Oct/2014. graf
Article in English | LILACS | 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.

Animals , Humans , Mice , Apoptosis/physiology , Carrier Proteins/metabolism , Mitochondrial Proteins/metabolism , Antibodies/metabolism , Antibodies/pharmacology , /metabolism , B-Lymphocytes/physiology , Caspase 9 , Cells, Cultured , Carrier Proteins/genetics , Caspases/metabolism , Enzyme Activation , Embryo, Mammalian/physiology , Gene Targeting , Intracellular Signaling Peptides and Proteins , Mice, Knockout , Mitochondrial Proteins/genetics , Survival Rate , Stem Cells/cytology , Stem Cells/metabolism , T-Lymphocytes/physiology
Indian J Biochem Biophys ; 2013 Oct; 50(5): 428-435
Article in English | IMSEAR | ID: sea-150252


Membrane repair is a conserved cellular process, where intracellular vesicles translocate to sites of plasma membrane injury to actively reseal membrane disruptions. Such membrane disruptions commonly occur in the course of normal physiology, particularly in skeletal muscles due to repeated contraction producing small tears in the sarcolemmal membrane. Here, we investigated whether prolonged exercise could produce adaptive changes in expression levels of proteins associated with the membrane repair process, including mitsugumin 53/tripartite motif-containing protein 72 (MG53/TRIM72), dysferlin and caveolin-3 (cav3). Mice were exercised using a treadmill running protocol and protein levels were measured by immunoblotting. The specificity of the antibodies used was established by immunoblot testing of various tissue lysates from both mice and rats. We found that MG53/TRIM72 immunostaining on isolated mouse skeletal muscle fibers showed protein localization at sites of membrane disruption created by the isolation of these muscle fibers. However, no significant changes in the expression levels of the tested membrane repair proteins were observed following prolonged treadmill running for eight weeks (30 to 80 min/day). These findings suggest that any compensation occurring in the membrane repair process in skeletal muscle following prolonged exercise does not affect the expression levels of these three key membrane repair proteins.

Animals , Carrier Proteins/metabolism , Caveolin 3/metabolism , Gene Expression Regulation , Male , Membrane Proteins/metabolism , Mice , Muscle, Skeletal/cytology , Muscle, Skeletal/physiology , Myocardium/cytology , Physical Conditioning, Animal , Protein Transport , Rats , Sarcolemma/metabolism , Time Factors
Article in English | WPRIM | ID: wpr-199828


We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs) vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8+ T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we revealed that RG-II activity is dependent on TLR4. RG-II showed a preventive effect of immunization with OVA-pulsed BMDCs against EG7 lymphoma. These results suggested that RG-II expedites the DC-based immune response through the TLR4 signaling pathway.

Acute-Phase Proteins/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Animals , Lipopolysaccharide Receptors/metabolism , Bone Marrow Cells/cytology , CD8-Positive T-Lymphocytes/immunology , Carrier Proteins/metabolism , Cell Differentiation/drug effects , Cell Nucleus/drug effects , Cell Proliferation/drug effects , Cytokines/biosynthesis , Dendritic Cells/cytology , Enzyme Activation/drug effects , Lymphocyte Activation/drug effects , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitogen-Activated Protein Kinases/metabolism , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Neoplasms/immunology , Pectins/pharmacology , Phenotype , Protein Transport/drug effects , Receptors, Chemokine/metabolism , Signal Transduction/drug effects , T-Lymphocytes, Cytotoxic/cytology , Toll-Like Receptor 4/agonists
Article in English | WPRIM | ID: wpr-170536


The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.

Bacterial Infections/immunology , Carrier Proteins/metabolism , Caspase 1/metabolism , Humans , Inflammasomes/immunology , Interleukin-1beta/metabolism , Signal Transduction
Mem. Inst. Oswaldo Cruz ; 107(supl.1): 174-182, Dec. 2012. ilus, graf
Article in English | LILACS | ID: lil-659756


When grown in the presence of exogenous collagen I, Mycobacterium bovis BCG was shown to form clumps. Scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. Since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed BCG cytoadherence in the presence of exogenous collagen I. Collagen increased the interaction of the bacilli with A549 type II pneumocytes or U937 macrophages, suggesting that BCG is able to recruit collagen to facilitate its attachment to host cells. Using an affinity chromatography approach, we have isolated a BCG collagen-binding protein corresponding to the previously described mycobacterial laminin-binding histone-like protein (LBP/Hlp), a highly conserved protein associated with the mycobacterial cell wall. Moreover, Mycobacterium leprae LBP/Hlp, a well-characterized adhesin, was also able to bind collagen I. Finally, using recombinant fragments of M. leprae LBP/Hlp, we mapped the collagen-binding activity within the C-terminal domain of the adhesin. Since this protein was already shown to be involved in the recognition of laminin and heparan sulphate-containing proteoglycans, the present observations reinforce the adhesive activities of LBP/Hlp, which can be therefore considered as a multifaceted mycobacterial adhesin, playing an important role in both leprosy and tuberculosis pathogenesis.

Animals , Humans , Bacterial Adhesion , Collagen Type I/pharmacology , Mycobacterium bovis/metabolism , Mycobacterium leprae/metabolism , Bacterial Adhesion/immunology , Carrier Proteins/immunology , Carrier Proteins/metabolism , Collagen Type I/metabolism , Histones/metabolism , Mycobacterium bovis/immunology , Mycobacterium leprae/immunology
Braz. j. med. biol. res ; 45(6): 557-564, June 2012. ilus, tab
Article in English | LILACS | ID: lil-622773


Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Adult , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Neoadjuvant Therapy/methods , Receptors, LDL/metabolism , Breast Neoplasms/metabolism , Carcinoma/metabolism , Carrier Proteins/metabolism , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Emulsions , Immunohistochemistry , Neoplasm Staging , Triglycerides/blood
Braz. j. med. biol. res ; 45(2): 113-117, Feb. 2012. ilus, tab
Article in English | LILACS | ID: lil-614577


Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes) in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ54 co-factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL). A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH4Cl) but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription.

Azospirillum brasilense/metabolism , Bacterial Proteins/metabolism , Nitrogen Fixation/genetics , Transcription Factors/metabolism , Azospirillum brasilense/chemistry , Azospirillum brasilense/genetics , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Carrier Proteins/genetics , Carrier Proteins/isolation & purification , Carrier Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/isolation & purification
Braz. j. med. biol. res ; 44(4): 283-290, Apr. 2011. ilus, tab
Article in English | LILACS | ID: lil-581495


Insertional mutagenesis is an important tool for functional genomics in Drosophila melanogaster. The insertion site in the KG00562 mutant fly line has been mapped to the CG8709 (herein named DmLpin) locus and to the 3’ of kermit (also called dGIPC). This mutant line presents a high lethality rate resulting from a gain of function. To obtain some insight into the biological role of the mutated locus, we have characterized the mutation and its relation to the high mortality of the KG00562 fly line. In this mutant, we did not detect one of the DmLpin transcripts, namely DmLpinK, but we did detect an unusual 2.3-kb mRNA (LpinK-w). Further investigation revealed that the LpinK-w transcript results from an aberrant splicing between the untranslated first exon of DmLpinK and the mini-white marker gene. Lack of DmLpinK or LpinK-w expression does not contribute to lethality, since heterozygous KG00562/Def7860 animals presented lethality rates comparable to those of the wild type. In contrast, the overexpression of kermit was associated with lethality of the KG00562 fly line. Significantly higher levels of kermit were detected in the Malpighian tubules of KG00562/+ flies that presented higher lethality rates than wild-type or KG00562/Def7860 animals, in which the lethality was rescued. In agreement with a recently reported study, our data support the hypothesis that misexpression of kermit/dGIPC could interfere with Drosophila development, with further investigations being needed in this direction.

Animals , Carrier Proteins/genetics , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Gene Expression/genetics , Mutation/genetics , Transcription, Genetic/genetics , Carrier Proteins/metabolism , Drosophila Proteins/metabolism , Malpighian Tubules/chemistry , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Transformation, Genetic