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Expression Levels of GABA-A Receptor Subunit Alpha 3, Gabra3 and Lipoprotein Lipase, Lpl Are Associated with the Susceptibility to Acetaminophen-Induced Hepatotoxicity
DC Field | Value | Language |
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dc.contributor.author | 남기택 | - |
dc.date.accessioned | 2017-11-02T08:39:04Z | - |
dc.date.available | 2017-11-02T08:39:04Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1976-9148 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/154717 | - |
dc.description.abstract | Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | Korean | - |
dc.publisher | Korean Society of Applied Pharmacology | - |
dc.relation.isPartOf | BIOMOLECULES & THERAPEUTICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Expression Levels of GABA-A Receptor Subunit Alpha 3, Gabra3 and Lipoprotein Lipase, Lpl Are Associated with the Susceptibility to Acetaminophen-Induced Hepatotoxicity | - |
dc.type | Article | - |
dc.publisher.location | Korea | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Life Science | - |
dc.contributor.googleauthor | Minjeong Kim | - |
dc.contributor.googleauthor | Jun-Won Yun | - |
dc.contributor.googleauthor | Kyeho Shin | - |
dc.contributor.googleauthor | Yejin Cho | - |
dc.contributor.googleauthor | Mijeong Yang | - |
dc.contributor.googleauthor | Ki Taek Nam | - |
dc.contributor.googleauthor | Kyung-Min Lim | - |
dc.identifier.doi | 10.4062/biomolther.2016.076. | - |
dc.contributor.localId | A01243 | - |
dc.relation.journalcode | J00324 | - |
dc.identifier.eissn | 2005-4483 | - |
dc.relation.journalsince | 2008~ | - |
dc.identifier.pmid | 27530116 | - |
dc.relation.journalbefore | ~2007 Journal of Applied Pharmacology | - |
dc.subject.keyword | Acetaminophen | - |
dc.subject.keyword | GABA-A receptor subunit alpha 3 | - |
dc.subject.keyword | Hepatotoxicity | - |
dc.subject.keyword | Lipoprotein lipase | - |
dc.subject.keyword | Toxicogenomics | - |
dc.contributor.alternativeName | Nam, Ki Taek | - |
dc.contributor.affiliatedAuthor | Nam, Ki Taek | - |
dc.citation.title | Biomolecules & Therapeutics | - |
dc.citation.volume | 25 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 112 | - |
dc.citation.endPage | 121 | - |
dc.identifier.bibliographicCitation | BIOMOLECULES & THERAPEUTICS, Vol.25(2) : 112-121, 2017 | - |
dc.date.modified | 2017-11-01 | - |
dc.identifier.rimsid | 44198 | - |
dc.type.rims | ART | - |
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