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Identification of Decrease in TRiC Proteins as Novel Targets of Alpha-Amanitin-Derived Hepatotoxicity by Comparative Proteomic Analysis In Vitro

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Abstract
Alpha-amanitin (alpha-AMA) is a cyclic peptide and one of the most lethal mushroom amatoxins found in Amanita phalloides. alpha-AMA is known to cause hepatotoxicity through RNA polymerase II inhibition, which acts in RNA and DNA translocation. To investigate the toxic signature of alpha-AMA beyond known mechanisms, we used quantitative nanoflow liquid chromatography-tandem mass spectrometry analysis coupled with tandem mass tag labeling to examine proteome dynamics in Huh-7 human hepatoma cells treated with toxic concentrations of alpha-AMA. Among the 1828 proteins identified, we quantified 1563 proteins, which revealed that four subunits in the T-complex protein 1-ring complex protein decreased depending on the alpha-AMA concentration. We conducted bioinformatics analyses of the quantified proteins to characterize the toxic signature of alpha-AMA in hepatoma cells. This is the first report of global changes in proteome abundance with variations in alpha-AMA concentration, and our findings suggest a novel molecular regulation mechanism for hepatotoxicity.
Author(s)
김도은김순주나안예손창환이상규이혜숙
Issued Date
2021
Type
Article
Keyword
alpha-amanitincomparative quantitative proteomicshepatotoxicityTRiC
DOI
10.3390/toxins13030197
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7926
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_d12f8450d3ca4c56ad9ee0dd37e18401&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Identification%20of%20Decrease%20in%20TRiC%20Proteins%20as%20Novel%20Targets%20of%20Alpha-Amanitin-Derived%20Hepatotoxicity%20by%20Comparative%20Proteomic%20Analysis%20In%20Vitro&offset=0&pcAvailability=true
Publisher
TOXINS
Location
스위스
Language
한국어
ISSN
2072-6651
Citation Volume
13
Citation Number
3
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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