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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-4
pubmed:abstractText
Recent studies have suggested a bystander effect in nonirradiated cells adjacent to irradiated cells; however, the mechanism is poorly understood. In this study, we investigated the involvement of both extracellular nucleotides and activation of P2 receptors in cellular responses to gamma radiation using human HaCaT keratinocytes. The concentration of ATP in culture medium was increased after gamma irradiation (0.1-1.0 Gy), suggesting that radiation induces ATP release from cells. Intracellular Ca(2+) concentration was elevated when conditioned medium from irradiated cells was transferred to nonirradiated cells, and this elevation was suppressed by apyrase (ecto-nucleotidase), indicating the involvement of extracellular nucleotides in this event. Further, we examined the activation of ERK1/2 by gamma radiation and nucleotides (ATP and UTP). Both gamma radiation and nucleotides induced activation of ERK1/2. Next, the effect of inhibitors of P2 receptors on radiation-induced activation of ERK1/2 was examined. The activation of ERK1/2 was blocked by suramin (P2Y inhibitor), MRS2578 (P2Y(6) antagonist) and apyrase. These results suggest that both released nucleotides and activation of P2Y receptors are involved in gamma-radiation-induced activation of ERK1/2. We conclude that ionizing radiation induces release of nucleotides from cells, leading to activation of P2Y receptors, which in turn would result in a variety of biological effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1938-5404
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
298-309
pubmed:meshHeading
pubmed-meshheading:20199215-Adenosine Triphosphate, pubmed-meshheading:20199215-Animals, pubmed-meshheading:20199215-Autocrine Communication, pubmed-meshheading:20199215-Calcium, pubmed-meshheading:20199215-Cell Line, pubmed-meshheading:20199215-Culture Media, Conditioned, pubmed-meshheading:20199215-Enzyme Activation, pubmed-meshheading:20199215-Extracellular Space, pubmed-meshheading:20199215-Gamma Rays, pubmed-meshheading:20199215-Humans, pubmed-meshheading:20199215-Intracellular Space, pubmed-meshheading:20199215-Keratinocytes, pubmed-meshheading:20199215-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20199215-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20199215-Paracrine Communication, pubmed-meshheading:20199215-Rats, pubmed-meshheading:20199215-Receptors, Purinergic P2, pubmed-meshheading:20199215-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
Involvement of purinergic signaling in cellular response to gamma radiation.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan. tsukim@rs.noda.tus.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't