Attenuated neurotoxicity of the transactivation-defective HIV-1 Tat protein in hippocampal cell cultures |
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Authors: | Michael Y Aksenov Marina V Aksenova Charles F Mactutus Rosemarie M Booze |
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Institution: | aProgram in Behavioral Neuroscience, University of South Carolina, SC 25908, USA |
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Abstract: | This study reports that the cysteine 22 → glycine 22 substitution in the HIV-1 Tat 1–86 B significantly attenuates its neurotoxicity. Consistent with previous studies, direct interactions of rat hippocampal cells with Tat 1–86 B were shown to cause dose-dependent and time-dependent neurotoxicity associated with activation of caspases from the mitochondrial apoptotic pathway. Despite the similar binding/uptake properties, Cys22 Tat 1–86 B failed to induce significant neurotoxicity and activation of caspases 9 and 3/7 in hippocampal primary cultures. Results of the study underscore the important role of cysteine-rich domain in mechanism of Tat-mediated neurotoxicity. |
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Keywords: | Hiv-1 Tat Neurotoxicity Cell culture Apoptosis Cysteine-rich domain |
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