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Article

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

1
BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea
2
BK21 Four-Sponsored Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea
3
Department of Emergency Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea
*
Authors to whom correspondence should be addressed.
Received: 7 February 2021 / Revised: 4 March 2021 / Accepted: 6 March 2021 / Published: 9 March 2021
Alpha-amanitin (α-AMA) is a cyclic peptide and one of the most lethal mushroom amatoxins found in Amanita phalloides. α-AMA is known to cause hepatotoxicity through RNA polymerase II inhibition, which acts in RNA and DNA translocation. To investigate the toxic signature of α-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 α-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 α-AMA concentration. We conducted bioinformatics analyses of the quantified proteins to characterize the toxic signature of α-AMA in hepatoma cells. This is the first report of global changes in proteome abundance with variations in α-AMA concentration, and our findings suggest a novel molecular regulation mechanism for hepatotoxicity. View Full-Text
Keywords: alpha-amanitin; comparative quantitative proteomics; TRiC; hepatotoxicity alpha-amanitin; comparative quantitative proteomics; TRiC; hepatotoxicity
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MDPI and ACS Style

Kim, D.; Kim, S.; Na, A.-Y.; Sohn, C.H.; Lee, S.; Lee, H.S. Identification of Decrease in TRiC Proteins as Novel Targets of Alpha-Amanitin-Derived Hepatotoxicity by Comparative Proteomic Analysis In Vitro. Toxins 2021, 13, 197. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030197

AMA Style

Kim D, Kim S, Na A-Y, Sohn CH, Lee S, Lee HS. Identification of Decrease in TRiC Proteins as Novel Targets of Alpha-Amanitin-Derived Hepatotoxicity by Comparative Proteomic Analysis In Vitro. Toxins. 2021; 13(3):197. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030197

Chicago/Turabian Style

Kim, Doeun; Kim, Sunjoo; Na, Ann-Yae; Sohn, Chang H.; Lee, Sangkyu; Lee, Hye S. 2021. "Identification of Decrease in TRiC Proteins as Novel Targets of Alpha-Amanitin-Derived Hepatotoxicity by Comparative Proteomic Analysis In Vitro" Toxins 13, no. 3: 197. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030197

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