دورية أكاديمية
أعرض في EDS

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

التفاصيل البيبلوغرافية
العنوان: Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.
المؤلفون: Hof WFJ; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., Visser M; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., de Jong JJ; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., Rajasekar MN; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., Schuringa JJ; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands., de Graaf IAM; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., Touw DJ; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands., Dekkers BGJ; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
المصدر: Toxins [Toxins (Basel)] 2024 Jan 22; Vol. 16 (1). Date of Electronic Publication: 2024 Jan 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101530765 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6651 (Electronic) Linking ISSN: 20726651 NLM ISO Abbreviation: Toxins (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Alpha-Amanitin*/toxicity , Mushroom Poisoning*, Humans ; Caspase 3 ; Antidotes/pharmacology ; Amanita
مستخلص: Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides , α- and β-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or β-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. β-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.
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فهرسة مساهمة: Keywords: Amanita phalloides; CD34+ stem cells; apoptosis; hematopoietic cell lines; α-amanitin
المشرفين على المادة: 0 (Alpha-Amanitin)
EC 3.4.22.- (Caspase 3)
0 (Antidotes)
SCR Organism: Amanita phalloides
تواريخ الأحداث: Date Created: 20240126 Date Completed: 20240129 Latest Revision: 20240227
رمز التحديث: 20240227
مُعرف محوري في PubMed: PMC10820516
DOI: 10.3390/toxins16010061
PMID: 38276537
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6651
DOI:10.3390/toxins16010061