title: Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage.
abstract: BACKGROUND
  Radiation exposure causes DNA damage, and DNA repair systems are essential to rescue damaged cells. Although DNA damage or oxidative stress activates transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) cation channels, it has not been established whether these TRP channels are involved in cellular responses to radiation-induced DNA damage. Here, we investigated the contribution of TRPM2 and TRPV1 channels to γ-irradiation- and UVB-induced DNA damage responses in human lung cancer A549 cells.
  
  
  METHODS
  A549 cells were irradiated with γ-rays (2.0Gy) or UVB (5-10mJ/cm(2)). γH2AX foci, ATM activation, 53BP1 accumulation and EGFR expression were evaluated by immunofluorescence staining. Extracellular ATP concentration was measured by luciferin-luciferase assay. Knockdown of TRPM2 and TRPV1 expression was done by siRNA transfection.
  
  
  RESULTS
  γ-Irradiation-induced γH2AX focus formation, ATM activation, 53BP1 accumulation and EGFR nuclear translocation, which are all associated with DNA repair, were suppressed by knockdown of TRPM2 and TRPV1 channels in A549 cells. Release of ATP, which mediates DNA damage response-associated activation of P2Y receptors, was suppressed by pre-treatment with catalase or knockdown of TRPM2 channel, but not TRPV1 channel. Similarly, UVB-induced γH2AX focus formation was suppressed in TRPM2- and TRPV1-knockdown cells, while UVB-induced ATP release was blocked in TRPM2- but not TRPV1-knockdown cells.
  
  
  CONCLUSIONS
  Our results suggest that the activation of TRPM2 channel, which mediates ATP release, and TRPV1 channel plays significant roles in the cellular responses to DNA damage induced by γ-irradiation and UVB irradiation.
  
  
  CONCLUSIONS
  Our results provide a new insight into the function of TRP channels from the viewpoint of radiation biology.
authors: Department of Radiation Biosciences, Tokyo University of Science, Noda-shi, Chiba, Japan.
authors: Kanako
authors: K
authors: Masumoto
authors: Mitsutoshi
authors: M
authors: Tsukimoto
authors: Shuji
authors: S
authors: Kojima
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage; D005720:Gamma Rays / Q000009:adverse effects*; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D000255:Adenosine Triphosphate