Apoptosis-like cell death in Leishmania donovani treated with KalsomeTM10, a new liposomal amphotericin B
| Autor: | Mohd Kamran, Nahid Ali, Baijayanti Jha, Mohammad Asad, Makaraju Deepthi, Md. Shadab |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Life Cycles Leishmania Donovani lcsh:Medicine Apoptosis DNA fragmentation DNA laddering Mitochondrion Protozoology Biochemistry White Blood Cells Mice Adenosine Triphosphate Animal Cells Medicine and Health Sciences lcsh:Science Amphotericin Protozoans Leishmania Membrane Potential Mitochondrial Multidisciplinary TUNEL assay Cell Death Antimicrobials Apoptotic DNA fragmentation Drugs Glutathione Endocytosis Cell biology Mitochondria Nucleic acids Cell Processes Caspases Protozoan Life Cycles Cellular Types Oxidation-Reduction Intracellular Research Article Amastigotes Programmed cell death Cell Survival Immune Cells Immunology Antiprotozoal Agents Mycology Phosphatidylserines Biology Nitric Oxide Microbiology 03 medical and health sciences Microbial Control Amphotericin B Genetics Parasitic Diseases Animals Pharmacology Antifungals Blood Cells Dose-Response Relationship Drug Promastigotes Macrophages lcsh:R Cell Membrane Organisms Biology and Life Sciences Cell Biology DNA Cell Cycle Checkpoints Molecular biology Parasitic Protozoans 030104 developmental biology lcsh:Q Lipid Peroxidation Reactive Oxygen Species Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 2, p e0171306 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Objective The present study aimed to elucidate the cell death mechanism in Leishmania donovani upon treatment with KalsomeTM10, a new liposomal amphotericin B. Methodology/Principal findings We studied morphological alterations in promastigotes through phase contrast and scanning electron microscopy. Phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and disruption of mitochondrial integrity was determined by flow cytometry using annexinV-FITC, JC-1 and mitotraker, respectively. For analysing oxidative stress, generation of H2O2 (bioluminescence kit) and mitochondrial superoxide O2− (mitosox) were measured. DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) and DNA laddering assay. We found that KalsomeTM10 is more effective then Ambisome against the promastigote as well as intracellular amastigote forms. The mechanistic study showed that KalsomeTM10 induced several morphological alterations in promastigotes typical of apoptosis. KalsomeTM10 treatment showed a dose- and time-dependent exposure of PS in promastigotes. Further, study on mitochondrial pathway revealed loss of mitochondrial membrane potential as well as disruption in mitochondrial integrity with depletion of intracellular pool of ATP. KalsomeTM10 treated promastigotes showed increased ROS production, diminished GSH levels and increased caspase-like activity. DNA fragmentation and cell cycle arrest was observed in KalsomeTM10 treated promastigotes. Apoptotic DNA fragmentation was also observed in KalsomeTM10 treated intracellular amastigotes. KalsomeTM10 induced generation of ROS and nitric oxide leads to the killing of the intracellular parasites. Moreover, endocytosis is indispensable for KalsomeTM10 mediated anti-leishmanial effect in host macrophage. Conclusions KalsomeTM10 induces apoptotic-like cell death in L. donovani parasites to exhibit its anti-leishmanial function. |
| Databáze: | OpenAIRE |
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