PubMed:26027517 JSON TXT

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TEST-CellLine

{"project":"TEST-CellLine","denotations":[{"id":"T1","span":{"begin":230,"end":235},"obj":"CellLine"},{"id":"T2","span":{"begin":646,"end":651},"obj":"CellLine"}],"attributes":[{"id":"A1","pred":"cellosaurus_accession_id","subj":"T1","obj":"CVCL_0343"},{"id":"A2","pred":"cellosaurus_accession_id","subj":"T2","obj":"CVCL_0343"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

TEST-DiseaseOrPhenotypicFeature

{"project":"TEST-DiseaseOrPhenotypicFeature","denotations":[{"id":"T1","span":{"begin":140,"end":156},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":991,"end":1000},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"D011832"},{"id":"A2","pred":"#label","subj":"T2","obj":"D014917"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

TEST-ChemicalEntity

{"project":"TEST-ChemicalEntity","denotations":[{"id":"T1","span":{"begin":206,"end":209},"obj":"ChemicalEntity"},{"id":"T2","span":{"begin":485,"end":492},"obj":"ChemicalEntity"},{"id":"T3","span":{"begin":991,"end":1006},"obj":"ChemicalEntity"},{"id":"T4","span":{"begin":1130,"end":1133},"obj":"ChemicalEntity"},{"id":"T5","span":{"begin":1476,"end":1479},"obj":"ChemicalEntity"},{"id":"T6","span":{"begin":1617,"end":1620},"obj":"ChemicalEntity"}],"attributes":[{"id":"A1","pred":"ID:","subj":"T1","obj":"http://purl.obolibrary.org/obo/CHEBI_80716"},{"id":"A2","pred":"ID:","subj":"T2","obj":"C512273"},{"id":"A3","pred":"ID:","subj":"T3","obj":"D037342"},{"id":"A4","pred":"ID:","subj":"T4","obj":"http://purl.obolibrary.org/obo/CHEBI_32386"},{"id":"A5","pred":"ID:","subj":"T5","obj":"http://purl.obolibrary.org/obo/CHEBI_80716"},{"id":"A6","pred":"ID:","subj":"T6","obj":"http://purl.obolibrary.org/obo/CHEBI_80716"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

TEST-OrganismTaxon

{"project":"TEST-OrganismTaxon","denotations":[{"id":"T1","span":{"begin":1405,"end":1409},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1425,"end":1429},"obj":"OrganismTaxon"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

Test-SequenceVariant

{"project":"Test-SequenceVariant","denotations":[{"id":"T1","span":{"begin":1014,"end":1019},"obj":"SequenceVariant"},{"id":"T2","span":{"begin":1020,"end":1025},"obj":"SequenceVariant"},{"id":"T3","span":{"begin":1026,"end":1031},"obj":"SequenceVariant"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

Test-GeneOrGeneProduct

{"project":"Test-GeneOrGeneProduct","denotations":[{"id":"T1","span":{"begin":4,"end":13},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":14,"end":18},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":19,"end":23},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":195,"end":204},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":206,"end":209},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":211,"end":215},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":216,"end":220},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":340,"end":344},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":430,"end":434},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":468,"end":479},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":510,"end":514},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":626,"end":630},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":758,"end":762},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":791,"end":795},"obj":"GeneOrGeneProduct"},{"id":"T15","span":{"begin":800,"end":804},"obj":"GeneOrGeneProduct"},{"id":"T16","span":{"begin":837,"end":841},"obj":"GeneOrGeneProduct"},{"id":"T17","span":{"begin":860,"end":864},"obj":"GeneOrGeneProduct"},{"id":"T18","span":{"begin":954,"end":958},"obj":"GeneOrGeneProduct"},{"id":"T19","span":{"begin":964,"end":968},"obj":"GeneOrGeneProduct"},{"id":"T20","span":{"begin":1001,"end":1006},"obj":"GeneOrGeneProduct"},{"id":"T21","span":{"begin":1062,"end":1066},"obj":"GeneOrGeneProduct"},{"id":"T22","span":{"begin":1110,"end":1114},"obj":"GeneOrGeneProduct"},{"id":"T23","span":{"begin":1136,"end":1141},"obj":"GeneOrGeneProduct"},{"id":"T24","span":{"begin":1144,"end":1149},"obj":"GeneOrGeneProduct"},{"id":"T25","span":{"begin":1327,"end":1331},"obj":"GeneOrGeneProduct"},{"id":"T26","span":{"begin":1397,"end":1401},"obj":"GeneOrGeneProduct"},{"id":"T27","span":{"begin":1476,"end":1479},"obj":"GeneOrGeneProduct"},{"id":"T28","span":{"begin":1587,"end":1591},"obj":"GeneOrGeneProduct"},{"id":"T29","span":{"begin":1617,"end":1620},"obj":"GeneOrGeneProduct"},{"id":"T30","span":{"begin":1625,"end":1629},"obj":"GeneOrGeneProduct"}],"text":"The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.\nIn this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1\u00263 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1\u00262 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair."}

Test-merged-2

Test-merged