Differential Induction of Rat Neuronal Excitotoxic Cell Death by Human Immunodeficiency Virus Type 1 Clade B and C Tat Proteins

摘要: In the absence of effective antiretroviral therapy, infection with clade B human immunodeficiency virus (HIV-1) commonly progresses to AIDS dementia. However, in India, where C is most prevalent, severe cognitive impairment due HIV-1 reported be less prevalent. The Tat protein HIV-1, which released from HIV-1-infected macrophages, thought play a major role disruption neuronal function as well infiltration macrophages associated advanced neuropathogenesis. Clade excitotoxic hippocampal neurons by potentiating N-methyl-d-aspartate-induced currents zinc-sensitive NR1/NR2A N-methyl-d-aspartate receptor zinc-binding-dependent mechanism. This study characterizes zinc-binding properties protein. Using ultraviolet spectroscopy and Ellman reaction, we show that binds just one zinc ion per monomer. We then investigated ability block inhibition receptors antagonism through chelation. Although enhanced N-methyl-d-aspartate-mediated rat hippocampus toxicity presence zinc, increase was significantly than observed Tat. These findings suggest differences neuropathogenesis found compared may, part, decrease Tat-mediated neurotoxicity.