Document Detail

Enhancement of zidovudine transfer to molt-4 cells, a human t-cell model, by dehydroepiandrosterone sulfate.
MedLine Citation:
PMID:  21574166     Owner:  NLM     Status:  Publisher    
A possible approach to improve antiretroviral therapy with nucleoside reverse transcriptase inhibitors is to enhance inhibitor delivery to CD4-positive T cells. We previously showed that dehydroepiandrosterone sulfate (DHEAS) enhances zidovudine (AZT) transfer into syncytiotrophoblast. Here, we investigated whether DHEAS also enhances AZT transfer into a cellular model of human T lymphocytes, and whether AZT is taken up by a specific transport system. The effects of DHEAS and related compounds on the uptake of [(3) H]AZT and other nucleosides by Molt-4 cells (a model of human CD4-positive T cells) were measured. [(3) H]AZT uptake by Molt-4 cells was nitrobenzylthioinosine insensitive and pH dependent, and the uptake was significantly inhibited by 1 mM ethylisopropylamiloride. [(3) H]AZT uptake by Molt-4 cells was increased in the presence of DHEAS, whereas uptake of other nucleosides was reduced. Kinetic study revealed that the maximum uptake velocity (up to 30 min) was increased in the presence of DHEAS. The structural requirements for AZT uptake-enhancing activity were studied using structural analogues of DHEAS. Estrone-3-sulfate and 16α-hydroxy DHEAS also enhanced AZT uptake into Molt-4 cells. The use of uptake enhancers may be a good strategy to improve the efficacy of antiretroviral therapy. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
Tomohiro Nishimura; Jun Tanaka; Masatoshi Tomi; Yoshiaki Seki; Noriko Kose; Yoshimichi Sai; Emi Nakashima
Related Documents :
17468216 - Analysis of leaf development in fugu mutants of arabidopsis reveals three compensation ...
6415366 - Enhancement of the spontaneous development of autoreactive b cells by ppd in mouse peri...
10537196 - Morphogenesis is coordinated with nuclear division in germinating aspergillus nidulans ...
16348716 - Preparation of refractile spores of clostridium thermosaccharolyticum involves a solven...
12664276 - Proteolysis and cell death in clover leaves is induced by grazing.
15963976 - Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by ...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-13
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  -     ISSN:  1520-6017     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: Clinica...
Next Document:  Hepatocyte proliferation and hepatomegaly induced by phenobarbital and 1,4-bis [2-(3,5-dichloropyrid...