Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP

Apurinic apyrimidinic endonuclease redox effector factor-1 (APE1/Ref-1) is involved both in the base excision repair (BER) of DNA lesions and in the eukaryotic transcriptional regulation. APE1/Ref-1 is regulated at both the transcriptional and post-translational levels, through control of subcellula...

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Main Authors:	Pines, Alex, Perrone, Lorena, Bivi, Nicoletta, Romanello, Milena, Damante, Giuseppe, Gulisano, Massimo, Kelley, Mark R., Quadrifoglio, Franco, Tell, Gianluca
Format:	Online
Language:	English
Published:	Oxford University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182699/

id	pubmed-1182699
recordtype	oai_dc
spelling	pubmed-11826992005-08-04 Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP Pines, Alex Perrone, Lorena Bivi, Nicoletta Romanello, Milena Damante, Giuseppe Gulisano, Massimo Kelley, Mark R. Quadrifoglio, Franco Tell, Gianluca Article Apurinic apyrimidinic endonuclease redox effector factor-1 (APE1/Ref-1) is involved both in the base excision repair (BER) of DNA lesions and in the eukaryotic transcriptional regulation. APE1/Ref-1 is regulated at both the transcriptional and post-translational levels, through control of subcellular localization and post-translational modification. In response to stress conditions, several cell types release ATP, which exerts stimulatory effects on eukaryotic cells via the purinergic receptors (P2) family. By using western blot and immunofluorescence analysis on a human tumour thyroid cell line (ARO), we demonstrate that purinergic stimulation by extracellular ATP induces quick cytoplasm to nucleus translocation of the protein at early times and its neosynthesis at later times. Continuous purinergic triggering by extracellular ATP released by ARO cells is responsible for the control of APE1/Ref-1 intracellular level. Interference with intracellular pathways activated by P2 triggering demonstrates that Ca2+ mobilization and intracellular reactive oxygen species (ROS) production are responsible for APE1/Ref-1 translocation. The APE1/Ref-1 activities on activator protein-1 (AP-1) DNA binding and DNA repair perfectly match its nuclear enrichment upon ATP stimulation. The biological relevance of our data is reinforced by the observation that APE1/Ref-1 stimulation by ATP protects ARO cells by H2O2-induced cell death. Our data provide new insights into the complex mechanisms regulating APE1/Ref-1 functions. Oxford University Press 2005 2005-08-02 /pmc/articles/PMC1182699/ /pubmed/16077024 http://dx.doi.org/10.1093/nar/gki751 Text en © The Author 2005. Published by Oxford University Press. All rights reserved
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Pines, Alex Perrone, Lorena Bivi, Nicoletta Romanello, Milena Damante, Giuseppe Gulisano, Massimo Kelley, Mark R. Quadrifoglio, Franco Tell, Gianluca
spellingShingle	Pines, Alex Perrone, Lorena Bivi, Nicoletta Romanello, Milena Damante, Giuseppe Gulisano, Massimo Kelley, Mark R. Quadrifoglio, Franco Tell, Gianluca Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
author_facet	Pines, Alex Perrone, Lorena Bivi, Nicoletta Romanello, Milena Damante, Giuseppe Gulisano, Massimo Kelley, Mark R. Quadrifoglio, Franco Tell, Gianluca
author_sort	Pines, Alex
title	Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
title_short	Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
title_full	Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
title_fullStr	Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
title_full_unstemmed	Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP
title_sort	activation of ape1/ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by atp
description	Apurinic apyrimidinic endonuclease redox effector factor-1 (APE1/Ref-1) is involved both in the base excision repair (BER) of DNA lesions and in the eukaryotic transcriptional regulation. APE1/Ref-1 is regulated at both the transcriptional and post-translational levels, through control of subcellular localization and post-translational modification. In response to stress conditions, several cell types release ATP, which exerts stimulatory effects on eukaryotic cells via the purinergic receptors (P2) family. By using western blot and immunofluorescence analysis on a human tumour thyroid cell line (ARO), we demonstrate that purinergic stimulation by extracellular ATP induces quick cytoplasm to nucleus translocation of the protein at early times and its neosynthesis at later times. Continuous purinergic triggering by extracellular ATP released by ARO cells is responsible for the control of APE1/Ref-1 intracellular level. Interference with intracellular pathways activated by P2 triggering demonstrates that Ca2+ mobilization and intracellular reactive oxygen species (ROS) production are responsible for APE1/Ref-1 translocation. The APE1/Ref-1 activities on activator protein-1 (AP-1) DNA binding and DNA repair perfectly match its nuclear enrichment upon ATP stimulation. The biological relevance of our data is reinforced by the observation that APE1/Ref-1 stimulation by ATP protects ARO cells by H2O2-induced cell death. Our data provide new insights into the complex mechanisms regulating APE1/Ref-1 functions.
publisher	Oxford University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182699/
_version_	1611376129125384192

Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP

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