Banca de QUALIFICAÇÃO: FABRÍCIA LIMA FONTES
Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.DISCENTE : FABRÍCIA LIMA FONTES
DATA : 03/08/2016
HORA: 14:00
LOCAL: SS1- Departamento de Biologia Celular e Genética
TÍTULO:
INHIBITION OF APE1/REF-1 REDOX FUNCTION BY E3330 REGULATES THE CELLULAR GROWTH AND RIBOSOME BIOGENESIS IN INFLAMMATION MODEL
PALAVRAS-CHAVES:
APE1/REF-1, redox function, rRNA processing, RelA(p65), c-Myc and ribosomal biogenesis
PÁGINAS: 40
RESUMO:
The multifunctional protein APE1/REF-1 plays an important role in the oxidative stress due to its DNA repair and transcriptional regulatory activities. Several studies have identified APE1/REF-1 related to cell growth, apoptosis, DNA damage, intracellular redox state, mitochondrial function, and cytoskeletal structure. However, it still remains a gap in the literature about how APE1/REF-1 regulates each activity. To identify genes preferentially regulated by redox function of APE1/REF-1, in this study was performed an extensive genome-wide survey using the high throughput RNA-Seq analysis of the LPS-stimulated U937 cells and subsequently treatment with E3330, a known inhibitor of the redox function of APE1/REF-1. Comparative transcriptome analysis revealed 1250 gene expression changes, 620 downregulated and 630 upregulated genes with absolute fold change ≥3 or ≤-3. The downregulated genes were found to be primarily involved in the regulation of ribosome biogenesis, gene expression and immune response, while the upregulated genes showed to be related with cellular response to stress, DNA repair and positive regulation of apoptosis. Further, the treatment with E3330 also promoted the reduction of several inflammatory modulators during time kinetics and cell viability decrease after 48 hours of treatment. Altogether, data point out a set of new purposes associated to the redox inhibition of APE1/REF-1 by E3330, such as difficulties the processing of rRNA, decreased transcription of RelA(p65), c-Myc, ribossomal genes leading to deficiency of ribosomal biogenesis and consequent growth arrest.
MEMBROS DA BANCA:
Interno - 2087759 - ANDRE DUCATI LUCHESSI
Interno - 1149647 - LUCYMARA FASSARELLA AGNEZ
Interno - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR