| pubmed-article:20061376 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0215343 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0000970 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0017037 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0017932 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0235378 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1366587 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1367731 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1510444 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1150587 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1705632 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C0599946 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:20061376 | lifeskim:mentions | umls-concept:C1517945 | lld:lifeskim |
| pubmed-article:20061376 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:20061376 | pubmed:dateCreated | 2010-3-8 | lld:pubmed |
| pubmed-article:20061376 | pubmed:abstractText | 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. | lld:pubmed |
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| pubmed-article:20061376 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20061376 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20061376 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:20061376 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20061376 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:20061376 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:KaplowitzNeil... | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:HanDerickD | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:GaardeWilliam... | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:JainShilpaS | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:WinSandaS | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:ThanTin... | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:ShinoharaMieM | lld:pubmed |
| pubmed-article:20061376 | pubmed:author | pubmed-author:YbanezMaria... | lld:pubmed |
| pubmed-article:20061376 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20061376 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:20061376 | pubmed:volume | 285 | lld:pubmed |
