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1.
Open Biol ; 6(6)2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27358292

RESUMO

Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using an optimal cut-off value of 162.65 pg ml(-1) revealed sensitivity and specificity for the diagnosis of lung adenocarcinoma of 88.7% and 85.7%, respectively, with an area under the curve of 0.927 (95% CI: 0.892 to 0.962, p < 0.0001). Serum UQCRH discriminates lung adenocarcinoma patients from the population without cancer with considerable sensitivity and specificity, but it does not distinguish between heavy smokers and lung adenocarcinoma patients. Serum UQCRH could be a potential diagnostic biomarker for lung adenocarcinoma.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Complexo III da Cadeia de Transporte de Elétrons/sangue , Neoplasias Pulmonares/sangue , Adenocarcinoma de Pulmão , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Curva ROC , Sensibilidade e Especificidade
2.
J Pain Symptom Manage ; 48(6): 1080-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24786901

RESUMO

OBJECTIVES: This prospective study explored relationships between expression changes of genes related to mitochondrial biogenesis/bioenergetics and fatigue in men with prostate cancer receiving external beam radiation therapy (EBRT). METHODS: Fatigue and gene expression were measured before (Day 0), at midpoint (Days 19-21), and at completion (Days 38-42) of EBRT using the seven-item Patient-Reported Outcomes Measurement Information System-Fatigue short form and from whole blood cell RNA, respectively. The human mitochondria RT2 Profiler PCR Array System was used to identify differential expression of mitochondrial biogenesis/bioenergetics-related genes. Mixed linear modeling estimated the changes in fatigue and gene expression over time and determined significant associations between gene expression and fatigue. RESULTS: Subjects were 50 men with prostate cancer (scheduled for EBRT = 25, active surveillance as matched controls = 25). The mean Patient-Reported Outcomes Measurement Information System-Fatigue T-score (mean = 50 ± 10 in a general population) for study subjects was 44.87 ± 5.89 and for controls was 43.5 ± 2.8 at baseline. Differential expression of two genes inside the mitochondria involved in critical mitochondrial complexes: BCS1L (ß = 1.30), SLC25A37 (ß = -2.44), and two genes on the outer mitochondrial membrane vital for mitochondrial integrity: BCL2L1 (ß = -1.68) and FIS1 (ß = -2.35) were significantly associated with changes in fatigue scores of study subjects during EBRT. CONCLUSION: Genes related to oxidative phosphorylation, energy production, and mitochondrial membrane integrity are associated with worsening fatigue during EBRT. Further investigation of the pathways involved with this association may explain mechanisms behind the development of fatigue in this population.


Assuntos
Fadiga/fisiopatologia , Mitocôndrias/metabolismo , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/radioterapia , ATPases Associadas a Diversas Atividades Celulares , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte de Cátions/sangue , Complexo III da Cadeia de Transporte de Elétrons/sangue , Metabolismo Energético/fisiologia , Metabolismo Energético/efeitos da radiação , Perfilação da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Mitocôndrias/efeitos da radiação , Proteínas Mitocondriais/sangue , Estudos Prospectivos , Índice de Gravidade de Doença , Proteína bcl-X/sangue
3.
Mol Cells ; 30(5): 393-401, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20811810

RESUMO

Ubiquinol-cytochrome c reductase complex chaperone (UQCC) involved in the development and maintenance of bone and cartilage is an important candidate gene for body measurement traits selection through marker-assisted selection (MAS). The expression of UQCC is upregulated in many human and animal models of height as well as other stature indexes. We have cloned the cDNA sequence coding UQCC gene in bovine. Genomic structural analysis indicated that bovine UQCC shares a high similarity with human UQCC. Furthermore, Real-Time PCR analysis show that the expression of bovine UQCC is remarkably different in diverse tissues, including high level expression in the spleen, heart and windpipe, and relatively low expression in other tissues. We also analyzed allele frequencies in different cattle breeds and an association study on the selected SNPs. SNP DraI A2691T in intron 1 and SNP Bsh1236I A3150G in intron 8 are significantly associated with Body Length (BL), Rump Length (RL), Chest Depth (CD) and Pin Bone Width (PBW). For the A2691T SNP marker, there are significant effects on the RL (p = 0.0001), CD (p = 0.0059) and PBW (p < 0.0001) in 679 individuals; with A3150G SNP marker, there are significant effects on the BL (p = 0.0047) and CD (p = 0.0454. Regarding association analysis of combination of the two SNPs, there are significant effects on the BL (p = 0.0215), CD (p = 0.0282) and PBW (p = 0.0329) in the total population. The results suggest that the UQCC gene is a candidate gene of body measurement traits in bovine reproduction and breeding, and provide data for establishing of an animal model using cattle to study big animal body type.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/fisiologia , Animais , Pesos e Medidas Corporais , Bovinos , Galinhas , Clonagem Molecular , DNA Complementar/genética , Complexo III da Cadeia de Transporte de Elétrons/sangue , Frequência do Gene/genética , Variação Genética , Genótipo , Humanos , Íntrons , Camundongos , Modelos Animais , Dados de Sequência Molecular , Pan troglodytes , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Alinhamento de Sequência , Análise de Sequência de DNA
4.
J Toxicol Clin Toxicol ; 41(3): 223-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12807302

RESUMO

OBJECTIVE: Chronic smoking has been associated with diverse mitochondrial respiratory chain (MRC) dysfunction in lymphocytes, although inhibition of complex IV activity is the most consistent and relevant finding. These mitochondrial abnormalities have been proposed to contribute to pathogenesis of diseases associated with tobacco consumption. We assessed MRC function in peripheral lymphocytes from heavy smokers after cessation in smoking habit. PATIENTS AND METHODS: We studied MRC function from peripheral lymphocytes of 10 healthy chronic smoker individuals (age 43 +/- 6 years; 50% women) before cessation of tobacco consumption (t0), and 7 (t1) and 28 (t2) days after cessation. Smoking abstinence was ascertained by measuring carboxyhemoglobin levels and carbon monoxide (CO) concentration in exhaled breath. Ten healthy nonsmoker individuals matched by age and gender were used as controls. Lymphocytes were isolated by Ficoll's gradient, and protein content was determined by Bradford's technique. MRC function was studied through double means: 1) individual enzyme activities of complex II, III, and IV were analyzed by means of spectrophotometry; 2) oxygen consumption was measured polarographically using pyruvate, succinate, and glycerol-3-phosphate (complex I, II, and III substrates, respectively) after lymphocyte permeabilization. Enzyme and oxidative activities were corrected by citrate synthase activity. RESULTS: Smokers showed a significant decrease in complex IV activity (p = 0.05) and also in respiration of intact lymphocytes (p = 0.05) compared to controls. Eight chronic smokers remained abstinent during the study. Smoking cessation was associated with a significant recovery of complex IV (p = 0.01) and complex III (p = 0.05) activities. Oxidative activities did not show any change during the study. CONCLUSION: Chronic smoking is associated with a decrease of complex IV and III activities of MRC, which return to normal values after cessation of tobacco smoking.


Assuntos
Linfócitos/enzimologia , Mitocôndrias/enzimologia , Doenças Mitocondriais/enzimologia , Consumo de Oxigênio/fisiologia , Abandono do Hábito de Fumar , Fumar/sangue , Adulto , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/sangue , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Feminino , Humanos , Linfócitos/fisiologia , Masculino , Mitocôndrias/fisiologia , Doenças Mitocondriais/sangue , Doenças Mitocondriais/etiologia , Oxirredução
5.
Mov Disord ; 12(1): 3-8, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8990047

RESUMO

Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in the substantia nigra in Parkinson's disease (PD) support the oxidative stress hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have found variable decreased CI and occasionally other complex activity suggestive of systemic impairment of MRC function in PD; however, MRC activity may be influenced by numerous variables. We conducted spectrophotometric measurements of MRC function in platelet mitochondrial preparations in 13 individuals with PD and 9 age-matched controls (CON) and have identified additional variables that may affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities were similar between PD and CON. CIII and CIV, specific and CS-corrected, activities were significantly positively correlated with CI in combined and individual group data, with the exception of CIII CS-corrected and CIV specific activities in CON and PD, respectively. CIII and CS specific activities were negatively correlated with age in CON, but varied randomly in PD. In PD, CIII specific activity was 1.4-fold higher in those with a history of environmental risk factors for PD and CIV specific activity was lower in those with a positive family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic properties of cells may thus contribute to conflicting data in studies of MRC function in platelets and other tissues.


Assuntos
Plaquetas/enzimologia , Transporte de Elétrons/fisiologia , Mitocôndrias/enzimologia , Doença de Parkinson/sangue , Adulto , Idoso , Citrato (si)-Sintase/sangue , Complexo III da Cadeia de Transporte de Elétrons/sangue , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NAD(P)H Desidrogenase (Quinona)/sangue , Valores de Referência
6.
Neurology ; 45(2): 344-8, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7854537

RESUMO

Previous studies have demonstrated impaired complex I activity in platelets from Parkinson's disease (PD) patients who were receiving levodopa and other medications for their disease. Eleven patients with early PD underwent three sequential plateletphereses: while on no medication, after receiving carbidopa/levodopa for 1 month, and after receiving carbidopa/levodopa plus selegiline for 1 additional month. As expected, carbidopa/levodopa and selegiline significantly improved motor function in these patients. Treatment with carbidopa/levodopa alone and carbidopa/levodopa plus selegiline did not affect the activities of complexes I, II/III, and IV and citrate synthetase. These observations support the hypothesis that impaired complex I activity in PD patients is a characteristic of the disease and not due to medications.


Assuntos
Plaquetas/enzimologia , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Mitocôndrias/enzimologia , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Selegilina/uso terapêutico , Adulto , Idoso , Análise de Variância , Plaquetas/efeitos dos fármacos , Citrato (si)-Sintase/sangue , Transporte de Elétrons , Complexo II de Transporte de Elétrons , Complexo III da Cadeia de Transporte de Elétrons/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Complexos Multienzimáticos/sangue , NAD(P)H Desidrogenase (Quinona)/sangue , Oxirredutases/sangue , Plaquetoferese , Succinato Desidrogenase/sangue
7.
Biochim Biophys Acta ; 936(1): 133-8, 1988 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-2846049

RESUMO

We have investigated electron transfer activities of respiratory chain complexes in platelet mitochondria of a patient with intermittent ataxia and lactic acidosis who was previously reported to be deficient in the E1 (decarboxylase) component of the pyruvate dehydrogenase complex. Electron transfer from succinate to cytochrome c was normal, but the mitochondria exhibited moderately decreased (63% of control) quinol: cytochrome-c oxidoreductase activity, suggesting a defect in complex III. Consistent with some perturbation in complex III, electron flux through complex III was resistant to inhibition by myxothiazol compared to normal controls. In contrast, titration with antimycin revealed a less abnormal pattern of inhibition. The extreme specificity of myxothiazol binding at or near the quinol oxidase domain of mitochondrial cytochrome b, i.e., b-566, suggests a defect in this region of complex III which may perturb the kinetics or thermodynamics of quinol oxidation in the complex. These data suggest that the patient's illness results from a mutation in the quinol oxidase domain of mitochondrial cytochrome b (b-566).


Assuntos
Ataxia/enzimologia , Plaquetas/ultraestrutura , Complexo III da Cadeia de Transporte de Elétrons/sangue , Mitocôndrias/efeitos dos fármacos , Acidose Láctica/sangue , Antimicina A/análogos & derivados , Antimicina A/farmacologia , Grupo dos Citocromos b/sangue , Grupo dos Citocromos b/genética , Resistência a Medicamentos , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons/efeitos dos fármacos , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Humanos , Hidroquinonas/metabolismo , Metacrilatos , Mitocôndrias/metabolismo , Mutação , Oxirredução , Doença da Deficiência do Complexo de Piruvato Desidrogenase/sangue , Doença da Deficiência do Complexo de Piruvato Desidrogenase/genética , Tiazóis/farmacologia
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