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dc.contributor.authorLyng, F M
dc.contributor.authorMaguire, P
dc.contributor.authorMcClean, B
dc.contributor.authorSeymour, C
dc.contributor.authorMothersill, C
dc.date.accessioned2017-05-29T14:45:53Z
dc.date.available2017-05-29T14:45:53Z
dc.date.issued2006-04
dc.identifier.citationThe involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects. 2006, 165 (4):400-9 Radiat. Res.en
dc.identifier.issn0033-7587
dc.identifier.pmid16579652
dc.identifier.urihttp://hdl.handle.net/10147/621399
dc.description.abstractMuch evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of bystander responses. Further investigations of these signaling pathways may aid in the identification of novel therapeutic targets.
dc.language.isoenen
dc.rightsArchived with thanks to Radiation researchen
dc.subjectBYSTANDER EFFECTSen
dc.subjectRADIATIONen
dc.subjectNEOPLASMSen
dc.subject.meshBystander Effect
dc.subject.meshCalcium
dc.subject.meshCalcium Signaling
dc.subject.meshCell Line
dc.subject.meshDose-Response Relationship, Radiation
dc.subject.meshHumans
dc.subject.meshKeratinocytes
dc.subject.meshMAP Kinase Signaling System
dc.subject.meshMitogen-Activated Protein Kinases
dc.subject.meshRadiation Dosage
dc.subject.meshSignal Transduction
dc.titleThe involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.en
dc.typeArticleen
dc.identifier.journalRadiation researchen
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen
refterms.dateFOA2018-08-27T21:26:21Z
html.description.abstractMuch evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of bystander responses. Further investigations of these signaling pathways may aid in the identification of novel therapeutic targets.


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