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1.
Pharmacol Rep ; 67(2): 345-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25712661

RESUMO

BACKGROUND: These studies aimed to identify the genes differentially expressed in the frontal cortex of mice treated repeatedly with either saline or desipramine (DMI). METHODS: Differences in gene expression in the mouse frontal cortex were studied using a whole-genome microarray approach. RESULTS: The analyses revealed a group of 88 transcripts (18 genes) that were differentially expressed between the mice treated with saline and those treated with DMI. These genes include Spnb2, Mef2c, Ncam1, Hsp90ab1, Kif1b, Ddx6 and Gsk3b, which were connected in the gene relationship network. CONCLUSIONS: It appears that one week of DMI administration measurably altered the expression of a small number of genes, including genes connected with neuroplasticity and cytoskeletal changes, the regulation of calcium levels in the cell or translation processes.


Assuntos
Desipramina/farmacologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Perfilação da Expressão Gênica , Expressão Gênica/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Masculino , Camundongos
2.
World J Gastroenterol ; 18(31): 4156-61, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22919248

RESUMO

AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the α subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman's coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson's coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies. CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis.


Assuntos
Hepatite B Crônica/metabolismo , Hepatite C Crônica/metabolismo , Fígado/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transcriptoma , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Adulto , Arrestinas/genética , Arrestinas/metabolismo , Biópsia , Cromograninas , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Hepatite B Crônica/genética , Hepatite B Crônica/patologia , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Estudos Retrospectivos , beta-Arrestinas
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