کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9425537 | 1295878 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular interactions of the type 1 human immunodeficiency virus transregulatory protein Tat with N-methyl-d-aspartate receptor subunits
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کلمات کلیدی
IndocarbocyanineFITCn.s.HBSCy3MK-801N-methyl-d-aspartateNMDABSA - BSAHEPES-buffered saline - HEPES-Buffered salinebovine serum albumin - آلبومین سرم گاوAIDS - ایدزTAT - تاتanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceDementia - جنون یا زوال عقلHAD - داشته استDizocilpine maleate - دیئوسیلپین مایناتNeurotoxicity - سمیت عصبیfluorescein isothiocyanate - فلوئورسین ایسوتیوسیاناتnot significant - مهم نیستHippocampus - هیپوکامپ HIV-1 - ویروس اچ آی وی نوع یکglutamate - گلوتامات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Molecular interactions of the type 1 human immunodeficiency virus transregulatory protein Tat with N-methyl-d-aspartate receptor subunits Molecular interactions of the type 1 human immunodeficiency virus transregulatory protein Tat with N-methyl-d-aspartate receptor subunits](/preview/png/9425537.png)
چکیده انگلیسی
We investigated the effect of type 1 human immunodeficiency virus (HIV-1) regulatory protein Tat on N-methyl-d-aspartate (NMDA) receptors expressed in Xenopus oocytes by voltage-clamp recording and its role in NMDA-mediated neurotoxicity using cultured rat hippocampal neurons. Tat (0.01-1μM) potentiated NMDA-induced currents of recombinant NMDA receptors. However, in the presence of Zn2+, the potentiating effect of Tat was much more pronounced, indicating an additional Zn2+-related effect on NMDA receptors. Consistently, Tat potentiated currents of the particularly Zn2+-sensitive NR1/NR2A NMDA receptor with a higher efficacy, whereas currents from a Zn2+-insensitive mutant were only marginally augmented. In addition, chemical-modified Tat, deficient for metal binding, did not reverse Zn2+-mediated inhibition of NMDA responses, demonstrating that Tat disinhibits NMDA receptors from Zn2+-mediated antagonism by complexing the cation. We therefore investigated the interplay of Tat and Zn2+ in NMDA-mediated neurotoxicity using cultures of rat hippocampal neurons. Zn2+ exhibited a prominent rescuing effect when added together with the excitotoxicant NMDA, which could be reverted by the Zn2+-chelator tricine. Similar to tricine, Tat enhanced NMDA-mediated neurotoxicity in the presence of neuroprotective Zn2+ concentrations. Double-staining with antibodies against Tat and the NR1 subunit of the NMDA receptor revealed partial colocalization of the immunoreactivities in membrane patches of hippocampal neurons, supporting the idea of a direct interplay between Tat and glutamatergic transmission. We therefore propose that release of Zn2+-mediated inhibition of NMDA receptors by HIV-1 Tat contributes to the neurotoxic effect of glutamate and may participate in the pathogenesis of AIDS-associated dementia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 134, Issue 1, 2005, Pages 145-153
Journal: Neuroscience - Volume 134, Issue 1, 2005, Pages 145-153
نویسندگان
T. Chandra, W. Maier, H.-G. König, K. Hirzel, D. Kögel, T. Schüler, A. Chandra, I. Demirhan, B. Laube,