Neurotoxicity of HIV-1 Tat protein: involvement of D1 dopamine receptor.
Neurotoxic viral proteins released from HIV-infected cells are believed to play a major role in the pathogenesis of the dementia displayed in a significant number of AIDS patients. HIV-1 associated neuropathology severely affects dopaminergic regions of the brain. Growing evidence indicates that HIV-1 neurotoxic proteins, such as Tat may affect the function of the dopamine transmission system. In turn, molecular components of dopamine neurotransmission may participate in a complex network of Tat-induced cell responses which result in neurodegeneration. In this study we investigated whether D1 dopamine receptors are involved in the mechanism of Tat neurotoxicity in primary rat neuronal cell cultures. We found that in rat midbrain cell cultures, which express significant levels of D1 dopamine receptors, the specific D1 antagonist SCH 23390 attenuates the cell death caused by HIV-1 Tat. In rat hippocampal cell cultures, where the expression of D1 receptors is low, SCH 23390 did not change the toxicity of Tat. Thus, the protective effect of SCH 23390 in rat primary neuronal cell cultures is a function of the level of D1 receptor protein expression. Our results provide further evidence for the involvement of the dopaminergic transmission system in the mechanism of HIV-1 Tat neurotoxicity.
Silvers
Janelle M
JM
Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.
Aksenova
Marina V
MV
Aksenov
Michael Y
MY
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008636:Mesencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; C470431:tat peptide (1-72), Human immunodeficiency virus 1; D014316:Tritium