alexa Apurinic endonuclease (Ref-1) is induced in mammalian cells by oxidative stress and involved in clastogenic adaptation.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Grsch S, Fritz G, Kaina B

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Abstract Apurinic endonuclease (APE; also known as Ref-1 protein) is a key enzyme in base excision repair, cleaving apurinic sites that arise spontaneously because of the activity of DNA glycosylases. To address the question of whether APE can be modulated by genotoxic stress affecting cellular protection, we analyzed the expression of APE in Chinese hamster ovary (CHO) cells after treatment with various genotoxic agents. We show that treatment of CHO cells with hydrogen peroxide (H2O2) or sodium hypochlorite (NaOCl) increases the levels of APE mRNA and protein. APE induction was observed 3-9 h after treatment and was accompanied by an increase in APE activity. We also show that the cloned human APE promoter transfected into CHO cells is stimulated by the oxidants, indicating transcriptional activation of the APE gene. When cells were pretreated with NaOCl, inducing APE, and then challenged with H2O2, the clastogenic effect of the challenge dose was significantly reduced, suggesting clastogenic adaptation due to APE induction. To further prove the involvement of APE in adaptation against induced chromosomal breakage, we transfected human APE cDNA driven by an inducible promoter into CHO cells and observed that transient induction of APE reduced the clastogenic effect of H2O2. Overall, the data demonstrate that the APE gene can be activated by oxidative agents, resulting in a transient increase in APE repair activity, which reduces the clastogenic response of cells to an oxidative agent. The protection of cells from chromosomal aberrations seen after prior exposure to oxidants is attributed to an adaptive response to oxidative stress.
This article was published in Cancer Res and referenced in Journal of Proteomics & Bioinformatics

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