Neuronal survival and resistance to HIV-1 Tat toxicity in the primary culture of rat fetal neurons.
In this study we report that primary cultures of rat fetal neurons contain subpopulations of cells that may be sensitive or resistant to HIV-1 Tat neurotoxicity. We demonstrate that rapid binding/uptake of Tat 1-86 for 2 h was sufficient to trigger caspase activation and neurodegeneration in rat fetal midbrain cell cultures. The uptake of Tat was followed by an increase in MCP1 (CCL2) immunoreactivity. Approximately 70% of neurons were able to survive transient or continuous (7 days) Tat exposure. The surviving neurons did not contain bound/internalized Tat, but were able to interact with Tat after medium replacement. These neurons were resistant to Tat toxicity. In neurons that resisted the toxic effects of continuous and repeated Tat treatment, levels of NR2A subunit of the NMDA receptor complex were significantly lower than in controls. We suggest that the subunit composition of NMDAR complexes may be important for the sensitivity of neurons to Tat toxicity.
Aksenova
Marina V
MV
Program in Behavioral Neuroscience, University of South Carolina, Columbia, SC 29208, USA.
Aksenov
Michael Y
MY
Adams
Sheila M
SM
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015696:Gene Products, tat / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000633:toxicity*
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D015696:Gene Products, tat; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D054322:tat Gene Products, Human Immunodeficiency Virus