Effects of Opiates and HIV Proteins on Neurons: The Role of Ferritin Heavy Chain and a Potential for Synergism

Festa, Lindsay; Meucci, Olimpia

doi:10.2174/157016212802138751

Cited by 14 publications

(11 citation statements)

References 132 publications

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“…Additional exploration of opioid–chemokine interactions has revealed that the heavy chain subunit of the ubiquitously expressed iron-binding protein ferritin (FHC) can act as a negative regulator of CXCR4 signaling (Festa & Meucci, 2012; Pitcher et al, 2014; Sengupta et al, 2009). This interaction is somewhat unusual, as ferritin has classically been described for its ability to sequester iron and for its role in iron homeostasis (Wang, Knovich, Coffman, Torti, & Torti, 2010).…”

Section: Cxcr4 Interactions With Opioidsmentioning

confidence: 99%

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

Nash

Meucci

2014

International Review of Neurobiology

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Activation of the G protein-coupled receptor CXCR4 by its chemokine ligand CXCL12 regulates a number of physiopathological functions in the central nervous system, during development as well as later in life. In addition to the more classical roles of the CXCL12/CXCR4 axis in the recruitment of immune cells or migration and proliferation of neural precursor cells, recent studies suggest that CXCR4 signaling also modulates synaptic function and neuronal survival in the mature brain, through direct and indirect effects on neurons and glia. These effects, which include regulation of glutamate receptors and uptake, and of dendritic spine density, can significantly alter the ability of neurons to face excitotoxic insults. Therefore, they are particularly relevant to neurodegenerative diseases featuring alterations of glutamate neurotransmission, such as HIV-associated neurocognitive disorders. Importantly, CXCR4 signaling can be dysregulated by HIV viral proteins, host HIV-induced factors, and opioids. Potential mechanisms of opioid regulation of CXCR4 include heterologous desensitization, transcriptional regulation and changes in receptor expression levels, opioid–chemokine receptor dimer or heteromer formation, and the newly described modulation by the protein ferritin heavy chain—all leading to inhibition of CXCR4 signaling. After reviewing major effects of chemokines and opioids in the CNS, this chapter discusses chemokine–opioid interactions in neuronal and immune cells, focusing on their potential contribution to HIV-associated neurocognitive disorders.

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Section: Cxcr4 Interactions With Opioidsmentioning

confidence: 99%

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

Nash

Meucci

2014

International Review of Neurobiology

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“…Incarcerated PLWH, particularly PWIDs, face enormous challenges accessing evidence-based HIV prevention interventions both within the criminal justice system and in the tumultuous period after release [15–17]. Furthermore, they disproportionally experience comorbid neurocognitive impairment (NCI) [18], alcohol use disorders (AUDs) [19, 20], and depressive symptoms [11, 21, 22], which may negatively impact their HRQoL. Without adequate treatment, support and related prevention services, these individuals are at greater risk of relapsing to drug use and related risk behaviors, not being linked to HIV care, and not achieving sufficient viral suppression to improve their health and reduce HIV transmission [23, 24].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis

et al. 2016

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Prior research has widely recognized neurocognitive impairment (NCI), depression, and alcohol use disorders (AUDs) as important negative predictors of health-related quality of life (HRQoL) among people living with HIV (PLWH). No studies to date, however, have explored how these neuropsychological factors operate together and affect HRQoL. Incarcerated male PLWH (N=301) meeting criteria for opioid dependence were recruited from Malaysia’s largest prison. Standardized scales for NCI, depression, alcohol use disorders (AUDs) and HRQoL were used to conduct a moderated mediation model to explore the extent to which depression mediated the relationship between NCI, HRQoL, and AUDs using an ordinary least squares regression-based path analytic framework. Results showed that increasing levels of NCI (B = −.1773, p<0.001) and depression (B = −.6147, p<0.001) were negatively associated with HRQoL. The effect of NCI on HRQoL was significantly (Sobel z = −3.5600, p < 0.001) mediated via depression (B = −.1230, p < 0.001). Furthermore, the conditional indirect effect of NCI on HRQoL via depression for individuals with AUDs was significant (B = −.9099, p = .0087), suggesting a moderated mediation effect. The findings disentangle the complex relationship using a moderated mediation model, demonstrating that increasing levels of NCI, which can be reduced with HIV treatment, negatively influenced HRQoL via depression for individuals with AUDs. This highlights the need for future interventions to target these complex interplay between neuropsychological factors in order to improve HRQoL among PLWH, particularly incarcerated PLWH with AUDs.

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“…Recent studies showed that the function of p53 not only depends on p53 overexpression but also depends on post-translational modification including methylation, acylation, phosphorylation and ubiquitination 37 . The interaction of gp120 and CXCR4 could result in cellular oxidative damage, which consequently activated p53 and increased Apaf-1 phosphorylation that mediated neuronal apoptosis 38 39 . In this study, Bax, the bcl-2 family member, has been confirmed to be involved in p53-mediated neurotoxicity induced by gp120 in primary cultured mouse cortical neurons, and our study also showed that the neurotoxicity induced by high doses of gp120 is associated with the translocation of ASPP2 from the cytoplasm to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons

Liu

Zang

Qiao

et al. 2016

Sci Rep

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The mechanisms behind HIV-1-associated neurocognitive disorders are still unclear. Apoptosis-stimulating protein 2 of p53 (ASPP2) is a damage-inducible p53-binding protein that stimulates p53-mediated apoptosis and transactivates proapoptotic and cell cycle regulatory genes. It has been reported that ASPP2 has a specific regulatory function in the death of retinal ganglion cells and the development of Alzheimer’s disease. In this study, we used p53 and ASPP2 knockout mice and primary cerebrocortical neuron culture to analyze the role of the interaction between ASPP2 with p53 in HIV-1 envelope glycoprotein gp120-induced neurotoxicity. The results showed that 10 ng/mL gp120 protein might stimulate p53 overexpression and translocation to the nucleus, and 30 ng/mL gp120 protein could stimulate both p53 and ASPP2 translocation to the nucleus, but only with p53 overexpression. The primary cultured neurons of p53−/−ASPP2+/− mice had a higher survival rate than p53−/− mice under gp120 protein stress. The interaction of ASPP2 with p53 induced by a high dose of gp120 stimulated Bax transcription and contributed to caspase-3 cleavage, and ASPP2-siRNA attenuated gp120 induced neuron death through inhibition of Bax expression. These results suggest that ASPP2 plays an important role in p53-mediated neuronal apoptosis under gp120 stress.

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Effects of Opiates and HIV Proteins on Neurons: The Role of Ferritin Heavy Chain and a Potential for Synergism

Cited by 14 publications

References 132 publications

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

Functions of the Chemokine Receptor CXCR4 in the Central Nervous System and Its Regulation by μ-Opioid Receptors

The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis

ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons

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