Attenuated neurotoxicity of the transactivation-defective HIV-1 Tat protein in hippocampal cell cultures.
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.
Aksenov
Michael Y
MY
Program in Behavioral Neuroscience, University of South Carolina, SC 25908, USA. aksenov@mailbox.sc.edu
Aksenova
Marina V
MV
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015696:Gene Products, tat; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D020169:Caspases; D003545:Cysteine