Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF- B in cells of the immune system

Rohr, Olivier; Sawaya, Bassel E.; Lecestre, Dominique; Aunis, Dominique; Schaeffer, Evelyne

doi:10.1093/nar/27.16.3291

Cited by 45 publications

(33 citation statements)

References 45 publications

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“…DA treatment was found to increase HIV replication in both peripheral blood mononuclear cells and Jurkat T cells transfected with a proviral HIV genome through activation of NF-B sites in the HIV-1 long terminal repeat. 69 Exposure to DA was also shown to enhance HIV replication in chronically infected ACH-2 T lymphoblasts, although this effect was abrogated in the presence of the antioxidant glutathione, suggesting that the enhancement was a product of oxidative stress. 70 Recent studies also demonstrated that treatment of MDMs with cocaine 23 or methamphetamine increased HIV replication and that D1R antagonists were able to abrogate the effects of methamphetamine treatment.…”

Section: Discussionmentioning

confidence: 98%

Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine

Gaskill

Calderon

Luers

et al. 2009

The American Journal of Pathology

120

130

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The prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) that result from HIV infection of the central nervous system is increasing. Macrophages, the primary target for HIV within the central nervous system, play a central role in HIV-induced neuropathogenesis. Drug abuse exacerbates HAND, but the mechanism(s) by which this increased neuropathology results in more severe forms of HAND in HIV-infected drug abusers is unclear. The addictive and reinforcing effects of many drugs of abuse, such as cocaine and methamphetamine, are mediated by increased extracellular dopamine in the brain. We propose a novel mechanism by which drugs of abuse intensify HIV neuropathogenesis through direct effects of the neurotransmitter dopamine on HIV infection of macrophages. We found that macrophages express dopamine receptors 1 and 2, and dopamine activates macrophages by increasing ERK 1 phosphorylation. Our results demonstrate for the first time that dopamine increases HIV replication in human macrophages and that the mechanism by which dopamine mediates this change is by increasing the total number of HIV-infected macrophages. This increase in HIV replication is mediated by activation of dopamine receptor 2. These findings suggest a common mechanism by which drugs of abuse enhance HIV replication in macrophages and indicate that the drug abuse-heightened levels of central nervous system dopamine could increase viral replication , thereby accelerating the development of HAND.

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Section: Discussionmentioning

confidence: 98%

Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine

Gaskill

Calderon

Luers

et al. 2009

The American Journal of Pathology

120

130

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“…However, caution is necessary due to reported effects of an enhanced CNS viral replication, induced CNS vacuolization, and encephalitic lesions with increased DA availability (i.e., administration of selegiline, an agent with DA and neuroprotective properties) (Czub et al, 2004). DA stimulated transcription through the NF-B element, specifically in the long terminal repeat, plays an important role in mediating DA responsiveness (Rohr et al, 1999). Thus, the possible implication of these findings for the use of D 1 supplements in the gp120 treatment of HIV-1-infected patients needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Intrahippocampal Glycoprotein 120 Injection: The Role of Dopaminergic Alterations in Prepulse Inhibition in Adult Rats

Fitting¹,

Booze²,

Mactutus³

2006

The Journal of Pharmacology and Experimental Therapeutics

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Following neonatal hippocampal administration on postnatal day 1, the dose-response effects of the human immunodeficiency virus 1 protein glycoprotein 120 (gp120) were studied in vivo on prepulse inhibition (PPI) in adulthood. Furthermore, the role of dopaminergic alterations was examined as a withinsubject factor. Using a randomized-block design, male and female pups of eight Sprague-Dawley litters were injected bilaterally with either vehicle (1 l volume) or gp120 (1.29, 12.9, or 129 ng/l). At 9 months of age, rats were injected s.c. with saline (SAL) (0.1 ml/kg) and tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by PPI of the auditory startle response (ASR) [interstimulus intervals (ISIs) of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin square design]. One month later, the animals were treated with a D 1 /D 2 agonist, apomorphine (APO) (0.1 mg/kg) and again tested for PPI. A significant attenuation of the baseline ASR by APO was noted. No significant effects were noted on control ASR trials (ISIs, 0 and 4000 ms). For the SAL condition, response inhibition was significantly reduced as a function of gp120 dose, and the inflection of the inhibition curve was significantly altered for the high-gp120 dose-treated animals. A gp120 treatment ϫ APO drug interaction was evident on amplitude, but not latency, of the response inhibition, with an enhanced inhibition in the APO condition, collapsed across ISIs (08 -120 ms) as the neonatal-injected gp120 dose increased. Use of APO to probe integrity of the dopaminergic system suggests long-lasting alterations in neuronal responses consequent to neonatal gp120 exposure.

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“…Previous studies indicated that stimulation of dopamine receptors results in NF-B activation (Rohr et al, 1999;Lee et al, 2001), but the role of individual dopamine receptors in this activation was not clear. We expressed human D2R (long) in HeLa cells, which lack an endogenous receptor for dopamine.…”

Section: Resultsmentioning

confidence: 99%

“…Purified D2R couples to the heterotrimeric G proteins G i 1, G i 2, and G i 3, and preferably activates G i 2 (Senogles et al, 1990), whereas in the brain, D2R preferentially couples to G o (Jiang et al, 2001). Several investigators recently reported that dopamine could induce NF-B activation in PC12, Jurkat, and Chinese hamster ovary cells, and contributes to regulation of apoptosis (Luo et al, 1999;Lee et al, 2001;Panet et al, 2001;Weingarten et al, 2001) and expression of HIV-1 genes (Rohr et al, 1999). However, the specific receptors and the underlying signaling mechanisms for this activity have not been characterized.…”

mentioning

confidence: 99%

Requirement of Gβγ and c-Src in D2 Dopamine Receptor-Mediated Nuclear Factor-κB Activation

Yang¹,

Zhang²,

Voyno-Yasenetskaya³

et al. 2003

Molecular Pharmacology

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The D2 dopamine receptor (D2R) was examined for its ability to mediate nuclear factor-B (NF-B) activation through G proteins. Stimulation of D2R-transfected HeLa cells with its agonist quinpirole induced the expression of a NF-B luciferase reporter and formation of NF-B-DNA complex. This response was blocked by pertussis toxin, and by the G␤␥ scavengers transducin and ␤-adrenergic receptor kinase 1 carboxyl-terminal fragment. Unlike G i -coupled chemoattractant receptors, D2R activated NF-B without an increase in phospholipase C-␤ activity, and the response was only slightly affected by the phosphoinositide 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). In contrast, treatment with genistein and 4-amino-1-tert-butyl-3-(p-methylphenyl)pyrazolo [3,4-d] pyrimidine abolished the induced NF-B activation, suggesting involvement of protein tyrosine kinases. Activation of D2R led to phosphorylation of c-Src at Tyr-418, and expression of a kinase-deficient c-Src inhibited D2R-mediated NF-B activation. The D2R-mediated NF-B activation was not dependent on epidermal growth factor (EGF) receptor transactivation since 4-(3Ј-chloroanilino)-6,7-dimethoxyquinazoline (AG1478), an EGF receptor-selective tyrphostin used at 1 M, blocked EGF-induced NF-B activation but not the quinpirole-induced response. In addition, the D2R-mediated NF-B activation was enhanced by over-expression of ␤-arrestin 1. These results suggest that D2R-mediated NF-B activation requires G␤␥ and c-Src, and possibly involves ␤-arrestin 1.The transcription factor nuclear factor B (NF-B) regulates the expression of a large number of genes coding for cytokines, growth factors, inducible effector enzymes, and regulators of apoptosis (reviewed in Ghosh et al., 1998). Activation of NF-B can be induced by a variety of environmental factors such as UV, as well as by cytokines such as TNF␣ and interleukin-1␤. The prototypical NF-B activation pathway, as seen in cells stimulated with TNF␣, involves inducible phosphorylation of IB␣ at Ser-32 and Ser-36 and subsequent degradation of this and similar inhibitory proteins.

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Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF- B in cells of the immune system

Cited by 45 publications

References 45 publications

Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine

Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine

Neonatal Intrahippocampal Glycoprotein 120 Injection: The Role of Dopaminergic Alterations in Prepulse Inhibition in Adult Rats

Requirement of Gβγ and c-Src in D2 Dopamine Receptor-Mediated Nuclear Factor-κB Activation

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