دورية أكاديمية
Identification of α-amanitin effector proteins in hepatocytes by limited proteolysis-coupled mass spectrometry.
| العنوان: | Identification of α-amanitin effector proteins in hepatocytes by limited proteolysis-coupled mass spectrometry. |
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| المؤلفون: | Kim D; College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea., Lee MS; BK21 Four-sponsored Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, Bucheon, 14662, Republic of Korea., Kim ND; Voronoibio Inc., Incheon, 21984, Republic of Korea., Lee S; School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: sangkyu@skku.edu., Lee HS; BK21 Four-sponsored Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. Electronic address: sianalee@catholic.ac.kr. |
| المصدر: | Chemico-biological interactions [Chem Biol Interact] 2023 Dec 01; Vol. 386, pp. 110778. Date of Electronic Publication: 2023 Oct 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| مواضيع طبية MeSH: | Alpha-Amanitin*/metabolism , Alpha-Amanitin*/toxicity , Hepatocytes*/metabolism, Humans ; Mice ; Animals ; Proteolysis ; Molecular Docking Simulation ; Mass Spectrometry |
| مستخلص: | The misuse of poisonous mushrooms containing amatoxins causes acute liver failure (ALF) in patients and is a cause of significant mortality. Although the toxic mechanisms of α-amanitin (α-AMA) and its interactions with RNA polymerase II (RNAP II) have been studied, α-AMA effector proteins that can interact with α-AMA in hepatocytes have not been systematically studied. Limited proteolysis-coupled mass spectrometry (LiP-MS) is an advanced technology that can quickly identify protein-ligand interactions based on global comparative proteomics. This study identified the α-AMA effector proteins found in human hepatocytes, following the detection of conformotypic peptides using LiP-MS coupled with tandem mass tag (TMT) technology. Proteins that are classified into protein processing in the endoplasmic reticulum and the ribosome during the KEGG pathway can be identified through affinity evaluation, according to α-AMA concentration-dependent LiP-MS and LiP-MS in hepatocytes derived from humans and mice, respectively. The possibility of interaction between α-AMA and proteins containing conformotypic peptides was evaluated through molecular docking studies. The results of this study suggest a novel path for α-AMA to induce hepatotoxicity through interactions with various proteins involved in protein synthesis, as well as with RNAP II. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hye Suk Lee reports financial support was provided by National Research Foundation of Korea. Sangkyu Lee reports financial support was provided by National Research Foundation of Korea. (Copyright © 2023. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Acute liver failure; Alpha-amanitin; Limited proteolysis-coupled mass spectrometry; Spliceosome; Toxic mushroom |
| المشرفين على المادة: | 0 (Alpha-Amanitin) |
| تواريخ الأحداث: | Date Created: 20231025 Date Completed: 20231120 Latest Revision: 20231120 |
| رمز التحديث: | 20231120 |
| DOI: | 10.1016/j.cbi.2023.110778 |
| PMID: | 37879594 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7786 |
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| DOI: | 10.1016/j.cbi.2023.110778 |