title: Extracellular ATP protects endothelial cells against DNA damage.
abstract: Cell damage can lead to rapid release of ATP to extracellular space resulting in dramatic change in local ATP concentration. Evolutionary, this has been considered as a danger signal leading to adaptive responses in adjacent cells. Our aim was to demonstrate that elevated extracellular ATP or inhibition of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be used to increase tolerance against DNA-damaging conditions. Human endothelial cells, with increased extracellular ATP concentration in cell proximity, were more resistant to irradiation or chemically induced DNA damage evaluated with the DNA damage markers γH2AX and phosphorylated p53. In our rat models of DNA damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage. Interestingly, the phenomenon could not be replicated in cancer cells. Our results show that transient increase in extracellular ATP can promote resistance to DNA damage.
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: Joonas
authors.initials: J
authors.lastname: Aho
authors.affiliation: Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Helenius
authors.affiliation: Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Vattulainen-Collanus
authors.affiliation: Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. tero-pekka.alastalo@helsinki.fi.
authors.forename: Tero-Pekka
authors.initials: TP
authors.lastname: Alastalo
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Koskenvuo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D015153:Blotting, Western; D004249:DNA Damage / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015703:Antigens, CD; D000255:Adenosine Triphosphate; D001081:Apyrase; C067869:CD39 antigen
keywords: ATP; CD39; Cancer; DNA damage; Endothelial cell; NTPDase1