| Regulatory role of nitric oxide in the reduced survival of erythrocytes in visceral leishmaniasis. | |
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MedLine Citation:
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PMID: 20576500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Nitric oxide (NO) plays a vital role in maintaining the survivability of circulating erythrocytes. Here we have investigated whether NO depletion associated with visceral leishmaniasis (VL) is responsible for the reduced survival of erythrocytes observed during the disease. METHODS: Infected hamsters were treated with standard anti-leishmanial sodium stibogluconate (SAG) and NO donor isosorbide dinitrate (ISD). Erythrophagocytosis by macrophages was determined by labelling the cells with FITC followed by flow cytometry. Aggregation of band3 was estimated from band3 associated EMA fluorescence. Caspase 3 activity was measured using immunosorbent assay kit. Phosphatidylserine (PS) externalization and cell shrinkage were determined using annexin V. Aminophspholipid translocase and scramblase activities were measured following NBD-PS and NBD-PC internalization, respectively. RESULTS: Impairment of both synthesis and uptake of NO resulted in decreased bioavailability of this signaling molecule in erythrocytes in VL. NO level was replenished after simultaneous treatment with ISD and SAG. Combination treatment decreased red cell apoptosis in infected animals by deactivating caspase 3 through s-nitrosylation. Drug treatment prevented infection-mediated ATP depletion and altered calcium homeostasis in erythrocytes. Improved metabolic environment effectively amended dysregulation of aminophospholipid translocase and scramblase, which in turn reduced cell shrinkage, and exposure of phosphatidylserine on the cell surface under the diseased condition. CONCLUSION AND GENERAL SIGNIFICANCE: In this study, we have identified NO depletion to be an important factor in promoting premature hemolysis with the progress of leishmanial infection. The study implicates NO to be a possible target for future drug development towards the promotion of erythrocyte survival in VL. |
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Authors:
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Kaustav Dutta Chowdhury; Gargi Sen; Tuli Biswas |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-26 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1800 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 964-76 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Indian Institute of Chemical Biology, CSIR, Kolkata-700032, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Anion Exchange Protein 1, Erythrocyte / metabolism Antimony Sodium Gluconate / pharmacology Antiprotozoal Agents / pharmacology Calcium / metabolism Caspase 3 / metabolism Cell Survival / drug effects Cricetinae Erythrocytes / metabolism*, parasitology Hemolysis / drug effects Humans Leishmania donovani* Leishmaniasis, Visceral / drug therapy, metabolism*, parasitology Macrophages / metabolism, parasitology Male Mesocricetus Nitric Oxide / metabolism* Phagocytosis / drug effects Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Anion Exchange Protein 1, Erythrocyte; 0/Antimony Sodium Gluconate; 0/Antiprotozoal Agents; 10102-43-9/Nitric Oxide; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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