| http://purl.uniprot.org/citations/30552702 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30552702 | http://www.w3.org/2000/01/rdf-schema#comment | "Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.org/dc/terms/identifier | "doi:10.1002/hep.30422"xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Chen D."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Ma X."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Yu J."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Ding W.X."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/author | "Ni H.M."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/name | "Hepatology"xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/pages | "2164-2179"xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/title | "p53 Up-regulated Modulator of Apoptosis Induction Mediates Acetaminophen-Induced Necrosis and Liver Injury in Mice."xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://purl.uniprot.org/core/volume | "69"xsd:string |
| http://purl.uniprot.org/citations/30552702 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30552702 |
| http://purl.uniprot.org/citations/30552702 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30552702 |
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