DISCENTE: RAYSSA KARLA DE MEDEIROS OLIVEIRA
LOCAL: Sala Carl Peter von Dietrich
The APE1 AP-sites repair activity is required for global immune response signalization at cellular models of inflammation.
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:
Presidente – LUCYMARA FASSARELLA AGNEZ
SELMA MARIA BEZERRA JERONIMO
VIVIAN NOGUEIRA SILBIGER