| http://purl.uniprot.org/citations/20061376 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20061376 | http://www.w3.org/2000/01/rdf-schema#comment | "Previously we demonstrated that c-Jun N-terminal kinase (JNK) plays a central role in acetaminophen (APAP)-induced liver injury. In the current work, we examined other possible signaling pathways that may also contribute to APAP hepatotoxicity. APAP treatment to mice caused glycogen synthase kinase-3beta (GSK-3beta) activation and translocation to mitochondria during the initial phase of APAP-induced liver injury ( approximately 1 h). The silencing of GSK-3beta, but not Akt-2 (protein kinase B) or glycogen synthase kinase-3alpha (GSK-3alpha), using antisense significantly protected mice from APAP-induced liver injury. The silencing of GSK-3beta affected several key pathways important in conferring protection against APAP-induced liver injury. APAP treatment was observed to promote the loss of glutamate cysteine ligase (GCL, rate-limiting enzyme in GSH synthesis) in liver. The silencing of GSK-3beta decreased the loss of hepatic GCL, and promoted greater GSH recovery in liver following APAP treatment. Silencing JNK1 and -2 also prevented the loss of GCL. APAP treatment also resulted in GSK-3beta translocation to mitochondria and the degradation of myeloid cell leukemia sequence 1 (Mcl-1) in mitochondrial membranes in liver. The silencing of GSK-3beta reduced Mcl-1 degradation caused by APAP treatment. The silencing of GSK-3beta also resulted in an inhibition of the early phase (0-2 h), and blunted the late phase (after 4 h) of JNK activation and translocation to mitochondria in liver following APAP treatment. Taken together our results suggest that activation of GSK-3beta is a key mediator of the initial phase of APAP-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.054999"xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Han D."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Jain S."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Shinohara M."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Kaplowitz N."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Win S."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Gaarde W.A."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Than T.A."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/author | "Ybanez M.D."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/pages | "8244-8255"xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/title | "Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1."xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/20061376 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20061376 |
| http://purl.uniprot.org/citations/20061376 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20061376 |
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| http://purl.uniprot.org/uniprot/#_A0A338P6P8-mappedCitation-20061376 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20061376 |
| http://purl.uniprot.org/uniprot/#_E9QAQ5-mappedCitation-20061376 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20061376 |
| http://purl.uniprot.org/uniprot/#_P97494-mappedCitation-20061376 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20061376 |
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| http://purl.uniprot.org/uniprot/#_Q9QZG5-mappedCitation-20061376 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20061376 |