دورية أكاديمية
Cell Death in Leishmania donovani promastigotes in response to Mammalian Aurora Kinase B Inhibitor- Hesperadin.
| العنوان: | Cell Death in Leishmania donovani promastigotes in response to Mammalian Aurora Kinase B Inhibitor- Hesperadin. |
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| المؤلفون: | Chhajer R; Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, India., Bhattacharyya A; Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, India., Ali N; Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700032, India. Electronic address: nali@iicb.res.in. |
| المصدر: | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Aug; Vol. 177, pp. 116960. Date of Electronic Publication: 2024 Jun 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982- |
| مواضيع طبية MeSH: | Leishmania donovani*/drug effects , Membrane Potential, Mitochondrial*/drug effects, Reactive Oxygen Species/metabolism ; Cell Death/drug effects ; Protein Kinase Inhibitors/pharmacology ; Mitochondria/drug effects ; Mitochondria/metabolism ; Apoptosis/drug effects ; Adenosine Triphosphate/metabolism ; Caspases/metabolism ; DNA Fragmentation/drug effects |
| مستخلص: | Deciphering how hesperadin, a repurposed mammalian aurora kinase B inhibitor, affects the cellular pathways in Leishmania donovani might be beneficial. This investigation sought to assess the physiological effects of hesperadin on promastigotes of L. donovani, by altering the duration of treatment following exposure to hesperadin. Groups pre-treated with inhibitors such as EGTA, NAC, and z-VAD-fmk before hesperadin exposure were also included. Morphological changes by microscopy, ATP and ROS changes by luminometry; DNA degradation using agarose gel electrophoresis and metacaspase levels through RT-PCR were assessed. Flow cytometry was used to study mitochondrial depolarization using JC-1 and MitoTracker Red; mitochondrial-superoxide accumulation using MitoSOX; plasma membrane modifications using Annexin-V and propidium iodide, and lastly, caspase activation using ApoStat. Significant alterations in promastigote morphology were noted. Caspase activity and mitochondrial-superoxide rose early after exposure whereas mitochondrial membrane potential demonstrated uncharacteristic variations, with significant functional disturbances such as leakage of superoxide radicals after prolonged treatments. ATP depletion and ROS accumulation demonstrated inverse patterns, genomic DNA showed fragmentation and plasma membrane showed Annexin-V binding, soon followed by propidium iodide uptake. Multilobed macronuclei and micronuclei accumulated in hesperadin exposed cells before they disintegrated into necrotic debris. The pathologic alterations were unlike the intrinsic or extrinsic pathways of classical apoptosis and suggest a caspase-mediated cell death most akin to mitotic-catastrophe. Most likely, a G2/M transition block caused accumulation of death signals, disorganized spindles and mechanical stresses, causing changes in morphology, organellar functions and ultimately promastigote death. Thus, death was a consequence of mitotic-arrest followed by ablation of kinetoplast functions, often implicated in L. donovani killing. Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest. (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Apoptosis; Aurora kinase; Cell-cycle; Hesperadin; Leishmania donovani; Mitotic-catastrophe |
| المشرفين على المادة: | 0 (Reactive Oxygen Species) 0 (Protein Kinase Inhibitors) 8L70Q75FXE (Adenosine Triphosphate) EC 3.4.22.- (Caspases) |
| تواريخ الأحداث: | Date Created: 20240627 Date Completed: 20240727 Latest Revision: 20240730 |
| رمز التحديث: | 20240731 |
| DOI: | 10.1016/j.biopha.2024.116960 |
| PMID: | 38936193 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1950-6007 |
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| DOI: | 10.1016/j.biopha.2024.116960 |