ATM Induces Cell Death with Autophagy in Response to H(2)O(2) Specifically in Caenorhabditis elegans Nondividing Cells

INTRODUCTION: Ataxia-telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response and is directly activated by reactive oxygen species (ROSs) in addition to DNA double-stranded breaks. However, the physiological function of the response to ROSs is not understood. PURPOSE: In the present study, we investigated how ATM responds to ROSs in Caenorhabditis elegans (C. elegans). MATERIALS AND METHODS: First, we measured sensitivities of larvae to DNA-damaging agents and ROSs. Next, we analyzed the drug sensitivities of fully matured adult worms, which consist of nondividing somatic cells. Dead cell staining with acridine orange was performed to visualize the dead cells. In addition, we performed GFP reporter assays of lgg-1, an autophagy-related gene, to determine the types of cell death. RESULTS: atm-1(tm5027) larvae showed a wide range of sensitivities to both DNA-damaging agents and ROSs. In contrast, fully matured adult worms, which consist of nondividing somatic cells, showed sensitivity to DNA-damaging agent, NaHSO(3), but they showed resistance to H(2)O(2). Dead cell staining and GFP reporter assays of lgg-1 suggest that C. elegans ATM-1 induces the cell death with autophagy in intestinal cells in response to H(2)O(2). CONCLUSION: We revealed that ATM induces cell death in response to H(2)O(2).