PubMed:12738769 JSONTXT

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":183,"end":440},"obj":"DRI_Challenge"},{"id":"T2","span":{"begin":441,"end":686},"obj":"DRI_Outcome"},{"id":"T3","span":{"begin":687,"end":909},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":910,"end":1154},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":1155,"end":1326},"obj":"DRI_Approach"},{"id":"T6","span":{"begin":1327,"end":1426},"obj":"DRI_Outcome"},{"id":"T7","span":{"begin":1454,"end":1525},"obj":"DRI_Outcome"},{"id":"T8","span":{"begin":1526,"end":1798},"obj":"DRI_Challenge"},{"id":"T9","span":{"begin":1799,"end":1962},"obj":"DRI_Outcome"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":182},"obj":"Sentence"},{"id":"T2","span":{"begin":183,"end":440},"obj":"Sentence"},{"id":"T3","span":{"begin":441,"end":686},"obj":"Sentence"},{"id":"T4","span":{"begin":687,"end":909},"obj":"Sentence"},{"id":"T5","span":{"begin":910,"end":1154},"obj":"Sentence"},{"id":"T6","span":{"begin":1155,"end":1326},"obj":"Sentence"},{"id":"T7","span":{"begin":1327,"end":1525},"obj":"Sentence"},{"id":"T8","span":{"begin":1526,"end":1798},"obj":"Sentence"},{"id":"T9","span":{"begin":1799,"end":1962},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":140,"end":151},"obj":"http://purl.obolibrary.org/obo/MAT_0000114"},{"id":"T2","span":{"begin":263,"end":268},"obj":"http://purl.obolibrary.org/obo/MAT_0000098"},{"id":"T3","span":{"begin":808,"end":819},"obj":"http://purl.obolibrary.org/obo/MAT_0000114"},{"id":"T4","span":{"begin":1142,"end":1153},"obj":"http://purl.obolibrary.org/obo/MAT_0000114"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":183,"end":190},"obj":"HP_0011034"},{"id":"T2","span":{"begin":234,"end":249},"obj":"HP_0100256"},{"id":"T3","span":{"begin":272,"end":291},"obj":"HP_0002511"},{"id":"T4","span":{"begin":314,"end":318},"obj":"HP_0000365"},{"id":"T5","span":{"begin":349,"end":362},"obj":"HP_0002529"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":182},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":183,"end":440},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":441,"end":686},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":687,"end":909},"obj":"DRI_Approach"},{"id":"T5","span":{"begin":910,"end":1154},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":1155,"end":1326},"obj":"DRI_Approach"},{"id":"T7","span":{"begin":1327,"end":1426},"obj":"DRI_Outcome"},{"id":"T8","span":{"begin":1427,"end":1453},"obj":"Token_Label.OUTSIDE"},{"id":"T9","span":{"begin":1454,"end":1525},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1526,"end":1798},"obj":"DRI_Challenge"},{"id":"T11","span":{"begin":1799,"end":1962},"obj":"DRI_Outcome"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":83,"end":90},"obj":"Disease"},{"id":"T2","span":{"begin":183,"end":190},"obj":"Disease"},{"id":"T3","span":{"begin":272,"end":291},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0004975"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":140,"end":151},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":808,"end":819},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":1142,"end":1153},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"72046"},{"id":"A2","pred":"db_id","subj":"T2","obj":"72046"},{"id":"A3","pred":"db_id","subj":"T3","obj":"72046"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":140,"end":151},"obj":"Body_part"},{"id":"T2","span":{"begin":263,"end":268},"obj":"Body_part"},{"id":"T3","span":{"begin":808,"end":819},"obj":"Body_part"},{"id":"T4","span":{"begin":1142,"end":1153},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000114"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000098"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000114"},{"id":"A4","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000114"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":140,"end":151},"obj":"Body_part"},{"id":"T4","span":{"begin":243,"end":249},"obj":"Body_part"},{"id":"T5","span":{"begin":263,"end":268},"obj":"Body_part"},{"id":"T7","span":{"begin":808,"end":819},"obj":"Body_part"},{"id":"T10","span":{"begin":877,"end":891},"obj":"Body_part"},{"id":"T11","span":{"begin":892,"end":900},"obj":"Body_part"},{"id":"T12","span":{"begin":1142,"end":1153},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0001954"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002421"},{"id":"A3","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002961"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0016482"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0000955"},{"id":"A6","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_6110636"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0001954"},{"id":"A8","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0002421"},{"id":"A9","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0002961"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL_0000598"},{"id":"A11","pred":"uberon_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/GO_0045202"},{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0001954"},{"id":"A13","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0002421"},{"id":"A14","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0002961"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":234,"end":249},"obj":"Phenotype"},{"id":"T2","span":{"begin":272,"end":291},"obj":"Phenotype"},{"id":"T3","span":{"begin":349,"end":362},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0100256"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0002511"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002529"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":349,"end":357},"obj":"Cell"},{"id":"T2","span":{"begin":577,"end":591},"obj":"Cell"},{"id":"T3","span":{"begin":877,"end":891},"obj":"Cell"},{"id":"T4","span":{"begin":1070,"end":1074},"obj":"Cell"},{"id":"T6","span":{"begin":1475,"end":1483},"obj":"Cell"},{"id":"T7","span":{"begin":1484,"end":1498},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000540"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000010"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000598"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000096"},{"id":"A5","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000775"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000540"},{"id":"A7","pred":"cl_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL:0000010"}],"text":"Activation of the c-Jun N-terminal kinase signaling cascade mediates the effect of amyloid-beta on long term potentiation and cell death in hippocampus: a role for interleukin-1beta?\nAmyloid-beta (Abeta) is a major constituent of the neuritic plaque found in the brain of Alzheimer's disease patients, and a great deal of evidence suggests that the neuronal loss that is associated with the disease is a consequence of the actions of Abeta. In the past few years, it has become apparent that activation of c-Jun N-terminal kinase (JNK) mediates some of the effects of Abeta on cultured cells; in particular, the evidence suggests that Abeta-triggered JNK activation leads to cell death. In this study, we investigated the effect of intracerebroventricular injection of Abeta(1-40) on signaling events in the hippocampus and on long term potentiation in Schaffer collateral CA1 pyramidal cell synapses in vivo. We report that Abeta(1-40) induced activation of JNK in CA1 and that this was coupled with expression of the proapoptotic protein, Bax, cytosolic cytochrome c, poly-(ADP-ribose) polymerase cleavage, and Fas ligand expression in the hippocampus. These data indicate that Abeta(1-40) inhibited expression of long term potentiation, and this effect was abrogated by administration of the JNK inhibitor peptide, D-JNKI1. In parallel with these findings, we observed that Abeta-induced changes in caspase-3 activation and TdT-mediated dUTP nick-end labeling staining in neuronal cultured cells were inhibited by D-JNKI1. We present evidence suggesting that interleukin (IL)-1beta plays a significant role in mediating the effects of Abeta(1-40) because Abeta(1-40) increased hippocampal IL-1beta and because several effects of Abeta(1-40) were inhibited by the caspase-1 inhibitor Ac-YVAD-CMK. On the basis of our findings, we propose that Abeta-induced changes in hippocampal plasticity are likely to be dependent upon IL-1beta-triggered activation of JNK."}