Evaluation of HIV-1 Tat induced neurotoxicity in rat cortical cell culture.
In a substantial number of cases, Human Immunodeficiency Virus type 1 (HIV-1) infection causes neuronal cell loss and leads to the development of AIDS associated dementia. Several studies have suggested that both host and viral factors contribute to neuronal loss. Here we studied the effect of HIV-1 Tat in primary rat neuronal cells as a model to understand mechanism of neuronal cell death. At nano molar concentration, recombinant Tat induced cell death in primary rat mixed cortical neurons. Tat could also induce uptake of calcium in primary rat cultures. When cells were incubated with NMDA receptor antagonists, MK-801 and D-CPP, cell death and 45Ca uptake were inhibited. Under similar conditions non-NMDA antagonists, NBQX, DNQX and CNQX, and sodium channel antagonist, TTX, did not inhibit Tat induced neuronal cell death. In a similar way HIV associated products from in vitro HIV-1 infected cells induced neuronal cell death which was inhibited by NMDA receptor antagonist. Results presented in this paper suggest that activation of NMDA receptors by HIV-1 Tat is responsible for neuronal cell death in primary rat cortical neurons.
Pérez
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A
Department of Infectious Diseases, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
Probert
A W
AW
Wang
K K
KK
Sharmeen
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L
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000633:toxicity*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D007163:Immunosorbent Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D017077:Culture Media, Conditioned; D016207:Cytokines; D018691:Excitatory Amino Acid Antagonists; D015696:Gene Products, tat; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D054322:tat Gene Products, Human Immunodeficiency Virus; C065286:SDZ EAA 494; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D002118:Calcium