Banca de QUALIFICAÇÃO: RAYSSA KARLA DE MEDEIROS OLIVEIRA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE: RAYSSA KARLA DE MEDEIROS OLIVEIRA
DATA: 06/06/2014
HORA: 14:00
LOCAL: Sala Carl Peter von Dietrich
TÍTULO:

The APE1 AP-sites repair activity is required for global immune response signalization at cellular models of inflammation.

PALAVRAS-CHAVES:

Methoxyamine, transcriptome, cytokines, autophagy.

PÁGINAS: 49
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

Base excision repair (BER) proteins have been associated with functions beyond DNA repair. Apurynic/apyrimidinic endonuclease 1 (APE1) is multifunctional proteins involved in a plethora of cellular activities, such as redox activation of transcription factors, RNA processing and DNA repair. In this work, bioinformatics analyses, and experimental approaches were employed to investigate the mechanisms by which inhibition of the AP-endonuclease activity of APE1 by methoxyamine (MX) modulates inflammatory response. The results demonstrated that the LPS/MX treatment reduced the expression of cytokines, chemokines and tool like receptors (TLR); and down-regulated immune biological processes, such as macrophage activation, NF-kB, TNF-α and interferon pathways, without induce cellular death. The transcriptomic results suggested that the LPS/MX treatment induced mitochondrion dysfunction, ER stress and autophagy pathways, probably activated by commitment of cellular energetics and/or DNA damage accumulation. In addition, it is propose that DNA repair activity of APE1 is necessary for transcription of inflammatory genes, by the interaction with abasic sites on specific promoters and recruitment of transcriptional complexes during inflammatory signalization. This work provide a new perspective about the interaction between BER activity and inflammatory response modulation, and suggests a novel role of APE1 protein as a redox independent modulator of immune response.

MEMBROS DA BANCA:
Interno - 1453487 - KATIA CASTANHO SCORTECCI
Presidente - 350647 - SELMA MARIA BEZERRA JERONIMO
Externo ao Programa - 1804884 - VIVIAN NOGUEIRA SILBIGER