کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4351473 1298055 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of HIV-1 tat-induced transactivation and apoptosis by the divalent metal chelators, fusaric acid and picolinic acid—Implications for HIV-1 dementia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Inhibition of HIV-1 tat-induced transactivation and apoptosis by the divalent metal chelators, fusaric acid and picolinic acid—Implications for HIV-1 dementia
چکیده انگلیسی

The HIV-1 transactivator protein tat is pivotal to the pathogenesis of AIDS, exerting its effects on both viral and cellular gene expression. The basic structure of tat protein allows it to be secreted by HIV-1 infected cells and penetrate uninfected cells where it elicits its multifunctional biochemical effects. The main function of tat protein is viral transactivation which leads to the upregulation of transcription through complex interactions with RNA and host cell factors. Since HIV-1 has been widely implicated as a causative agent of HIV-1 dementia, the aim of our study was to investigate the ability of two novel metal chelators, fusaric acid (FA) and picolinic acid (PA) to firstly inhibit HIV-1 tat induced transcription and secondly, to minimize its cytotoxic effects as mediated via apoptosis. Biologically active tat protein is not freely available commercially. We therefore had to produce, isolate and purify our own protein. A cell culture system and flow cytometric techniques were used in our study. Exposure of CEM-GFP cells to exogenous recombinant tat protein induced transcription and apoptosis, and both processes were inhibited by FA and PA at concentrations that alone did not induce any cytotoxicity. Our data suggest that FA and PA may have therapeutic potential in the management of HIV-1 dementia.


► We used two metal ion chelators to inhibit tat protein induced transactivation and apoptosis.
► The inhibition of apoptosis and transactivation was not due to the inhibition of the cell cycle.
► Chelation therapy using fusaric acid and picolinic acid may have implications for HIV-1 dementia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Research - Volume 74, Issue 1, September 2012, Pages 59–63
نویسندگان
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