Regulatory Role of Nitric Oxide in the Reduced Survival of Erythrocytes in Visceral Leishmaniasis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Regulatory Role of Nitric Oxide in the Reduced Survival of Erythrocytes in Visceral Leishmaniasis
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| Creator |
Dutta Chowdhury, Kaustav
Sen, Gargi Biswas, Tuli |
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| Subject |
Cell Biology & Physiology
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| Description |
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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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/979/1/24_bba_2010.pdf
Dutta Chowdhury, Kaustav and Sen, Gargi and Biswas, Tuli (2010) Regulatory Role of Nitric Oxide in the Reduced Survival of Erythrocytes in Visceral Leishmaniasis. Biochimica et Biophysica Acta, 1800 (9). pp. 964-976. |
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| Relation |
http://dx.doi.org/10.1016/j.bbagen.2010.05.008
http://www.eprints.iicb.res.in/979/ |
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