| S-allyl cysteine in combination with clotrimazole downregulates Fas induced apoptotic events in erythrocytes of mice exposed to lead. | |
| | |
MedLine Citation:
|
PMID: 22033380 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
BACKGROUND: Chronic lead (Pb(2+)) exposure leads to the reduced lifespan of erythrocytes. Oxidative stress and K(+) loss accelerate Fas translocation into lipid raft microdomains inducing Fas mediated death signaling in these erythrocytes. Pathophysiological-based therapeutic strategies to combat against erythrocyte death were evaluated using garlic-derived organosulfur compounds like diallyl disulfide (DADS), S allyl cysteine (SAC) and imidazole based Gardos channel inhibitor clotrimazole (CLT). METHODS: Morphological alterations in erythrocytes were evaluated using scanning electron microscopy. Events associated with erythrocyte death were evaluated using radio labeled probes, flow cytometry and activity gel assay. Mass spectrometry was used for detection of GSH-4-hydroxy-trans-2-nonenal (HNE) adducts. Fas redistribution into the lipid rafts was studied using immunoblotting technique and confocal microscopy. RESULTS: Combination of SAC and CLT was better than DADS and CLT combination and monotherapy with these agents in prolonging the survival of erythrocytes during chronic Pb(2+) exposure. Combination therapy with SAC and CLT prevented redistribution of Fas into the lipid rafts of the plasma membrane and downregulated Fas-dependent death events in erythrocytes of mice exposed to Pb(2+). CONCLUSION AND GENERAL SIGNIFICANCE: Ceramide generation was a critical component of Fas receptor-induced apoptosis, since inhibition of acid sphingomyelinase (aSMase) interfered with Fas-induced apoptosis during Pb(2+) exposure. Combination therapy with SAC and CLT downregulated apoptotic events in erythrocytes by antagonizing oxidative stress and Gardos channel that led to suppression of ceramide-initiated Fas aggregation in lipid rafts. Hence, combination therapy with SAC and CLT may be a potential therapeutic option for enhancing the lifespan of erythrocytes during Pb(2+) toxicity. |
| | |
Authors:
|
Samir Mandal; Sudip Mukherjee; Kaustav Dutta Chowdhury; Avik Sarkar; Kankana Basu; Soumosish Paul; Debasish Karmakar; Mahasweta Chatterjee; Tuli Biswas; Gobinda Chandra Sadhukhan; Gargi Sen |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-14 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: - ISSN: 0006-3002 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
|
Indian Institute of Chemical Biology (CSIR), 4, Raja S.C. Mullick Road, Kolkata-700032, India. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Analysis of IP(3) receptors in and out of cells.
Next Document: [Factors that contribute to health care associated infections: how to prevent them].