دورية أكاديمية
Amanitin-induced variable cytotoxicity in various cell lines is mediated by the different expression levels of OATP1B3.
| العنوان: | Amanitin-induced variable cytotoxicity in various cell lines is mediated by the different expression levels of OATP1B3. |
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| المؤلفون: | Gong M; School of Agriculture, Yangtze University, Jingzhou, 434025, China; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Li Z; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Xu H; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Ma B; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Gao P; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Wang L; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China., Li J; School of Agriculture, Yangtze University, Jingzhou, 434025, China., Wu Q; School of Agriculture, Yangtze University, Jingzhou, 434025, China. Electronic address: wql106@163.com., Wu J; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China. Electronic address: ammswjf@hotmail.com., Xie J; Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China. Electronic address: xiejw@bmi.ac.cn. |
| المصدر: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2024 Jun; Vol. 188, pp. 114665. Date of Electronic Publication: 2024 Apr 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 8207483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6351 (Electronic) Linking ISSN: 02786915 NLM ISO Abbreviation: Food Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Exeter : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1982- |
| مواضيع طبية MeSH: | Solute Carrier Organic Anion Transporter Family Member 1B3*/metabolism , Solute Carrier Organic Anion Transporter Family Member 1B3*/genetics , Amanitins*/toxicity, Humans ; HEK293 Cells ; Cell Line ; Cell Survival/drug effects ; Alpha-Amanitin/toxicity ; Hep G2 Cells |
| مستخلص: | Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides, amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, β, and γ-amanitin at concentrations ranging from 0.3 to 100 μM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Amanitin; Apoptosis; Cytotoxicity; Mode of cell death; OATP1B3; Organ toxicity |
| المشرفين على المادة: | 0 (Solute Carrier Organic Anion Transporter Family Member 1B3) 0 (Amanitins) 0 (SLCO1B3 protein, human) 0 (Alpha-Amanitin) |
| تواريخ الأحداث: | Date Created: 20240419 Date Completed: 20240513 Latest Revision: 20240513 |
| رمز التحديث: | 20240514 |
| DOI: | 10.1016/j.fct.2024.114665 |
| PMID: | 38641045 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-6351 |
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| DOI: | 10.1016/j.fct.2024.114665 |