Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury ROLE OF GAP JUNCTION DYSFUNCTION AND CONNEXIN 32 MISLOCALIZATION
DC Field | Value | Language |
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dc.contributor.author | Park, Woo-Jae | - |
dc.contributor.author | Park, Joo-Won | - |
dc.contributor.author | Erez-Roman, Racheli | - |
dc.contributor.author | Kogot-Levin, Aviram | - |
dc.contributor.author | Bame, Jessica R. | - |
dc.contributor.author | Tirosh, Boaz | - |
dc.contributor.author | Saada, Ann | - |
dc.contributor.author | Merrill, Alfred H., Jr. | - |
dc.contributor.author | Pewzner-Jung, Yael | - |
dc.contributor.author | Futerman, Anthony H. | - |
dc.date.available | 2020-02-28T22:45:07Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2013-10-25 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14209 | - |
dc.description.abstract | Very long chain (C22-C24) ceramides are synthesized by ceramide synthase 2 (CerS2). A CerS2 null mouse displays hepatopathy because of depletion of C22-C24 ceramides, elevation of C16-ceramide, and/or elevation of sphinganine. Unexpectedly, CerS2 null mice were resistant to acetaminophen-induced hepatotoxicity. Although there were a number of biochemical changes in the liver, such as increased levels of glutathione and multiple drug-resistant protein 4, these effects are unlikely to account for the lack of acetaminophen toxicity. A number of other hepatotoxic agents, such as D-galactosamine, CCl4, and thioacetamide, were also ineffective in inducing liver damage. All of these drugs and chemicals require connexin (Cx) 32, a key gap junction protein, to induce hepatotoxicity. Cx32 was mislocalized to an intracellular location in hepatocytes from CerS2 null mice, which resulted in accelerated rates of its lysosomal degradation. This mislocalization resulted from the altered membrane properties of the CerS2 null mice, which was exemplified by the disruption of detergent-resistant membranes. The lack of acetaminophen toxicity and Cx32 mislocalization were reversed upon infection with recombinant adeno-associated virus expressing CerS2. We establish that Gap junction function is compromised upon altering the sphingolipid acyl chain length composition, which is of relevance for understanding the regulation of drug-induced liver injury. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.subject | FUMONISIN B-1 TOXICITY | - |
dc.subject | MEDIATED GENE-TRANSFER | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | LIPID RAFTS | - |
dc.subject | ACETAMINOPHEN HEPATOTOXICITY | - |
dc.subject | INTERCELLULAR COMMUNICATION | - |
dc.subject | SPHINGOLIPID METABOLISM | - |
dc.subject | INSULIN-RESISTANCE | - |
dc.subject | TERMINAL KINASE | - |
dc.subject | MICE | - |
dc.title | Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury ROLE OF GAP JUNCTION DYSFUNCTION AND CONNEXIN 32 MISLOCALIZATION | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000330778900011 | - |
dc.identifier.doi | 10.1074/jbc.M112.448852 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.288, no.43, pp.30904 - 30916 | - |
dc.identifier.scopusid | 2-s2.0-84886687848 | - |
dc.citation.endPage | 30916 | - |
dc.citation.startPage | 30904 | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 288 | - |
dc.citation.number | 43 | - |
dc.contributor.affiliatedAuthor | Park, Woo-Jae | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | FUMONISIN B-1 TOXICITY | - |
dc.subject.keywordPlus | MEDIATED GENE-TRANSFER | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | LIPID RAFTS | - |
dc.subject.keywordPlus | ACETAMINOPHEN HEPATOTOXICITY | - |
dc.subject.keywordPlus | INTERCELLULAR COMMUNICATION | - |
dc.subject.keywordPlus | SPHINGOLIPID METABOLISM | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | TERMINAL KINASE | - |
dc.subject.keywordPlus | MICE | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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