ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2012
HIV-1 Tat protein decreases dopamine transporter cell surface expression and vesicular monoamine transporter-2 function in rat striatal synaptosomes.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 56 citations in OpenAlex.
- HIV-1 Tat expression drives progressive synaptic decline: evidence from longitudinal [NeuroImmune pharmacology and therapeutics · 2026Article
- HIV-1 Tat and gp120 as key drivers of neurodegeneration in the central nervous system.Frontiers in microbiology · 2026Review
- Impact of HIV-1 tat protein on methamphetamine-induced inhibition of vesicular monoamine transporter2-mediated dopamine transport and methamphetamine conditioned place preference in HIV-1 tat transgenic mice.European journal of pharmacology · 2024Article
- Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.Biomolecules & therapeutics · 2024Review
- HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.Journal of neurochemistry · 2024Article
- A helping HAND: therapeutic potential of MAGL inhibition against HIV-1-associated neuroinflammation.Frontiers in immunology · 2024Article
- Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine.Cellular and molecular neurobiology · 2023Article
- Novel Allosteric Modulator Southern Research Institute-32743 Reverses HIV-1 Transactivator of Transcription-Induced Increase in Dopamine Release in the Caudate Putamen of Inducible Transactivator of Transcription Transgenic Mice.The Journal of pharmacology and experimental therapeutics · 2023Article
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Deprenyl reduces inflammation during acute SIV infection.iScience · 2022Article
- Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection.Microorganisms · 2021Review
- HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies.Open biology · 2020Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- [The Journal of pharmacology and experimental therapeutics · 2020Article
- Article
- Cross-talk between microglia and neurons regulates HIV latency.PLoS pathogens · 2019Article
- Selective monoaminergic and histaminergic circuit dysregulation following long-term HIV-1 protein exposure.Journal of neurovirology · 2019Article
- Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Scaling Synapses in the Presence of HIV.Neurochemical research · 2019Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The dopamine (DA) transporter (DAT) and vesicular monoamine transporter (VMAT2) proteins interact as a biochemical complex to regulate dopaminergic neurotransmission. We have reported that HIV-1Tat(1-86) decreases the specific [(3)H]DA uptake and [(3)H]WIN 35,428 binding sites without a change in total DAT immunoreactivity in rat striatum (Zhu et al., 2009b). The present study determined the effects of Tat on DAT phosphorylation and trafficking, and vesicular [(3)H]DA uptake. Pre-incubation of rat striatal synaptosomes with the protein kinase C (PKC) inhibitor bisindolylmaleimide I (1 μM) completely blocked Tat(1-86)-induced reduction of [(3)H]DA uptake, indicating that Tat regulates DAT function through a PKC-dependent mechanism. After exposure of synaptosomes to Tat(1-86) (1 μM), DAT immunoreactivity was decreased in plasma membrane enriched fractions (P3) and increased in vesicle-enriched fractions (P4) relative to controls without change in total synaptosomal fractions (P2), suggesting that Tat-induced inhibition of DA uptake is attributable to DAT internalization. Although both DAT and VMAT2 proteins are essential for the regulation of DA disposition in synapse and cytosol, Tat inhibited the specific [(3)H]DA uptake into vesicles (P4) and synaptosomes (P2) by 35 % and 26 %, respectively, inferring that the inhibitory effect of Tat was more profound in VMAT2 protein than in DAT protein. Taken together, the current study reveals that Tat inhibits DAT function through a PKC and trafficking-dependent mechanism and that Tat impacts the dopaminergic tone by regulating both DAT and VMAT2 proteins. These findings provide new insight into understanding the pharmacological mechanisms of HIV-1 viral protein-induced dysfunction of DA neurotransmission in HIV-infected patients.
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