PubMed:25006961 JSON TXT

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LitCoin-entities

LitCoin-entities-OrganismTaxon-PD

{"project":"LitCoin-entities-OrganismTaxon-PD","denotations":[{"id":"T1","span":{"begin":552,"end":556},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":659,"end":663},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":768,"end":772},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":931,"end":935},"obj":"OrganismTaxon"},{"id":"T9","span":{"begin":1101,"end":1105},"obj":"OrganismTaxon"},{"id":"T11","span":{"begin":1308,"end":1312},"obj":"OrganismTaxon"},{"id":"T13","span":{"begin":1484,"end":1488},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"NCBItxid:10095"},{"id":"A2","pred":"db_id","subj":"T1","obj":"NCBItxid:10088"},{"id":"A3","pred":"db_id","subj":"T3","obj":"NCBItxid:10095"},{"id":"A4","pred":"db_id","subj":"T3","obj":"NCBItxid:10088"},{"id":"A5","pred":"db_id","subj":"T5","obj":"NCBItxid:10095"},{"id":"A6","pred":"db_id","subj":"T5","obj":"NCBItxid:10088"},{"id":"A7","pred":"db_id","subj":"T7","obj":"NCBItxid:10095"},{"id":"A8","pred":"db_id","subj":"T7","obj":"NCBItxid:10088"},{"id":"A9","pred":"db_id","subj":"T9","obj":"NCBItxid:10095"},{"id":"A10","pred":"db_id","subj":"T9","obj":"NCBItxid:10088"},{"id":"A11","pred":"db_id","subj":"T11","obj":"NCBItxid:10095"},{"id":"A12","pred":"db_id","subj":"T11","obj":"NCBItxid:10088"},{"id":"A13","pred":"db_id","subj":"T13","obj":"NCBItxid:10095"},{"id":"A14","pred":"db_id","subj":"T13","obj":"NCBItxid:10088"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-sentences

{"project":"LitCoin-sentences","denotations":[{"id":"T1","span":{"begin":0,"end":79},"obj":"Sentence"},{"id":"T2","span":{"begin":80,"end":182},"obj":"Sentence"},{"id":"T3","span":{"begin":183,"end":395},"obj":"Sentence"},{"id":"T4","span":{"begin":396,"end":536},"obj":"Sentence"},{"id":"T5","span":{"begin":537,"end":655},"obj":"Sentence"},{"id":"T6","span":{"begin":656,"end":820},"obj":"Sentence"},{"id":"T7","span":{"begin":821,"end":976},"obj":"Sentence"},{"id":"T8","span":{"begin":977,"end":1029},"obj":"Sentence"},{"id":"T9","span":{"begin":1030,"end":1081},"obj":"Sentence"},{"id":"T10","span":{"begin":1082,"end":1205},"obj":"Sentence"},{"id":"T11","span":{"begin":1206,"end":1382},"obj":"Sentence"},{"id":"T12","span":{"begin":1383,"end":1489},"obj":"Sentence"},{"id":"T13","span":{"begin":1490,"end":1695},"obj":"Sentence"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin_Mondo

{"project":"LitCoin_Mondo","denotations":[{"id":"T1","span":{"begin":48,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":60,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":125,"end":155},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":137,"end":155},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0016383"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0004782"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0016383"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0004782"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-GeneOrGeneProduct-v0

LitCoin-GeneOrGeneProduct-v2

LitCoin-Disease-MeSH

{"project":"LitCoin-Disease-MeSH","denotations":[{"id":"T1","span":{"begin":48,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":125,"end":155},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":527,"end":535},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":571,"end":577},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1654,"end":1662},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"originalLabel","subj":"T1","obj":"D018500"},{"id":"A2","pred":"originalLabel","subj":"T2","obj":"D018500"},{"id":"A3","pred":"originalLabel","subj":"T3","obj":"D011141"},{"id":"A4","pred":"originalLabel","subj":"T4","obj":"D013180"},{"id":"A5","pred":"originalLabel","subj":"T5","obj":"D011141"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-GeneOrGeneProduct-v3

{"project":"LitCoin-GeneOrGeneProduct-v3","denotations":[{"id":"T1","span":{"begin":11,"end":20},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":48,"end":78},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":125,"end":155},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":157,"end":160},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":313,"end":329},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":331,"end":336},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":342,"end":355},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":357,"end":361},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":448,"end":451},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":537,"end":546},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":558,"end":561},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":760,"end":763},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":857,"end":861},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":946,"end":950},"obj":"GeneOrGeneProduct"},{"id":"T15","span":{"begin":968,"end":971},"obj":"GeneOrGeneProduct"},{"id":"T16","span":{"begin":1012,"end":1017},"obj":"GeneOrGeneProduct"},{"id":"T17","span":{"begin":1157,"end":1160},"obj":"GeneOrGeneProduct"},{"id":"T18","span":{"begin":1206,"end":1210},"obj":"GeneOrGeneProduct"},{"id":"T19","span":{"begin":1215,"end":1220},"obj":"GeneOrGeneProduct"},{"id":"T20","span":{"begin":1300,"end":1303},"obj":"GeneOrGeneProduct"},{"id":"T21","span":{"begin":1314,"end":1318},"obj":"GeneOrGeneProduct"},{"id":"T22","span":{"begin":1350,"end":1355},"obj":"GeneOrGeneProduct"},{"id":"T23","span":{"begin":1476,"end":1479},"obj":"GeneOrGeneProduct"},{"id":"T24","span":{"begin":1521,"end":1524},"obj":"GeneOrGeneProduct"},{"id":"T25","span":{"begin":1536,"end":1540},"obj":"GeneOrGeneProduct"},{"id":"T26","span":{"begin":1545,"end":1550},"obj":"GeneOrGeneProduct"},{"id":"T27","span":{"begin":1551,"end":1569},"obj":"GeneOrGeneProduct"},{"id":"T28","span":{"begin":1606,"end":1609},"obj":"GeneOrGeneProduct"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin_Mondo_095

{"project":"LitCoin_Mondo_095","denotations":[{"id":"T1","span":{"begin":48,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":125,"end":155},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":1446,"end":1449},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":1472,"end":1475},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0016383"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0016383"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0007620"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0007620"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-MeSH-Disease-2

{"project":"LitCoin-MeSH-Disease-2","denotations":[{"id":"T1","span":{"begin":48,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":125,"end":155},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":527,"end":535},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":571,"end":577},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1654,"end":1662},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"ID:","subj":"T1","obj":"D018500"},{"id":"A2","pred":"ID:","subj":"T2","obj":"D018500"},{"id":"A3","pred":"ID:","subj":"T3","obj":"D011141"},{"id":"A4","pred":"ID:","subj":"T4","obj":"D013180"},{"id":"A5","pred":"ID:","subj":"T5","obj":"D011141"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-MONDO_bioort2019

{"project":"LitCoin-MONDO_bioort2019","denotations":[{"id":"T1","span":{"begin":48,"end":78},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":125,"end":155},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":527,"end":535},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":1654,"end":1662},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"D018500"},{"id":"A2","pred":"#label","subj":"T2","obj":"D018500"},{"id":"A3","pred":"#label","subj":"T3","obj":"D011141"},{"id":"A4","pred":"#label","subj":"T4","obj":"D011141"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-Chemical-MeSH-CHEBI

LitCoin-NCBITaxon-2

{"project":"LitCoin-NCBITaxon-2","denotations":[{"id":"T1","span":{"begin":173,"end":181},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":552,"end":556},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":659,"end":663},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":768,"end":772},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":931,"end":935},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":1101,"end":1105},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":1308,"end":1312},"obj":"OrganismTaxon"},{"id":"T8","span":{"begin":1484,"end":1488},"obj":"OrganismTaxon"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

LitCoin-training-merged

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":125,"end":155},"obj":"HP_0009806"},{"id":"T2","span":{"begin":137,"end":155},"obj":"HP_0000873"},{"id":"T3","span":{"begin":527,"end":535},"obj":"HP_0000103"},{"id":"T4","span":{"begin":668,"end":690},"obj":"HP_0000103"},{"id":"T5","span":{"begin":1118,"end":1140},"obj":"HP_0000103"},{"id":"T6","span":{"begin":1654,"end":1662},"obj":"HP_0000103"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_25006961_1_0","span":{"begin":125,"end":155},"obj":"expanded"},{"id":"SS2_25006961_1_0","span":{"begin":157,"end":160},"obj":"abbr"},{"id":"SS1_25006961_4_0","span":{"begin":586,"end":595},"obj":"expanded"},{"id":"SS2_25006961_4_0","span":{"begin":597,"end":599},"obj":"abbr"}],"relations":[{"id":"AE1_25006961_1_0","pred":"abbreviatedTo","subj":"SS1_25006961_1_0","obj":"SS2_25006961_1_0"},{"id":"AE1_25006961_4_0","pred":"abbreviatedTo","subj":"SS1_25006961_4_0","obj":"SS2_25006961_4_0"}],"text":"Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.\nLithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."}