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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

Title
Expression levels of GABA-A receptor subunit alpha 3, Gabra3 and lipoprotein lipase, Lpl are associated with the susceptibility to acetaminophen-induced hepatotoxicity
Authors
Kim M.Yun J.-W.Shin K.Cho Y.Yang M.Nam K.T.Lim K.-M.
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2017
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
Biomolecules and Therapeutics vol. 25, no. 2, pp. 112 - 121
Keywords
AcetaminophenGABA-A receptor subunit alpha 3HepatotoxicityLipoprotein lipaseToxicogenomics
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS; KCI WOS scopus
Document Type
Article
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. © 2017 The Korean Society of Applied Pharmacology.
DOI
10.4062/biomolther.2016.076
Appears in Collections:
약학대학 > 약학과 > Journal papers
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