Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T

Buzy, Jeanine M.; Brenneman, Douglas E.; Pert, Candace B.; Martin, Alex; Salazar, Andrés M.; Ruff, Michael R.

doi:10.1016/0006-8993(92)90161-2

Cited by 44 publications

(11 citation statements)

References 40 publications

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“…Gp120 has been reported to be present in the CNS of HIV-infected patients [10]. Additionally, gp120 is reported to cause increased oxidative stress in the brain [11], increase the BBB permeability [12], [13], increase the cell-death [3], [14], [15] and increase the expression of proinflammatory cytokines and chemokines such as IL-6, IL-8, IL-1β, and CCL5 in astrocytes and neurons [16], [17], [18], [19].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Cooperation between Methamphetamine and HIV-1 gsp120 through the P13K/Akt Pathway Induces IL-6 but not IL-8 Expression in Astrocytes

et al. 2012

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HIV-1 envelope protein gp120 has been extensively studied for neurotoxic effects that have been attributed to the increased expression of various proinflammatory cytokines in the CNS. Recently we have shown that methamphetamine (MA) also increases expression of proinflammatory cytokines in astrocytes. However, combined effect of gp120 and MA is not known. The present study was undertaken to determine cumulative effect and the mechanism(s)/pathways involved in the functional interaction between gp120 and MA in SVGA astrocytes. Our results clearly suggest that gp120 and MA affect IL-6 but not IL-8 in a synergistic manner and this synergy was mediated by PI3K/Akt and NF-κB pathways. Inhibition of either of these pathways could abrogate the increased expression of IL-6 due to MA or gp120 alone, as well as the increased expression of IL-6 when the astrocytes were treated with both gp120 and MA. These results were confirmed by both, using chemical inhibitors/siRNA as well as western blotting. This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes.

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Section: Introductionmentioning

confidence: 99%

Synergistic Cooperation between Methamphetamine and HIV-1 gsp120 through the P13K/Akt Pathway Induces IL-6 but not IL-8 Expression in Astrocytes

et al. 2012

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“…The gp120 may have been stripped off and it must go somewhere, so we suspect that there is a low level of gp120 in the brain. Buzy and colleagues 74 reported that antibodies that cross-react with gp120 blocked the neuronkilling effect of cerebrospinal fluid from a patient with AIDS dementia, also suggesting that low levels of gp120 were present.…”

Section: Discussionmentioning

confidence: 99%

Dementia Associated with the Acquired Immunodeficiency Syndrome

Lipton

Gendelman²

1995

N Engl J Med

443

223

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“…These data also suggest that the potential growth-retarding effects of gp120 will vary depending on the concentration of gp120 and the stage in development in which exposure occurs. gp120 has been measured at concentrations from 1.0-7.6 ϫ 10 Ϫ 10 M in the serum of AIDS patients (47), and potent neurotoxicity has been observed in the cerebrospinal fluid of HIV-infected patients (48). The above concentrations are within the range at which we show a significant effect on embryonic growth.…”

Section: Discussionmentioning

confidence: 61%

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

Dibbern¹,

Glazner²,

Gozes³

et al. 1997

J. Clin. Invest.

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Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10 Ϫ 8 M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers.

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Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T

Cited by 44 publications

References 40 publications

Synergistic Cooperation between Methamphetamine and HIV-1 gsp120 through the P13K/Akt Pathway Induces IL-6 but not IL-8 Expression in Astrocytes

Synergistic Cooperation between Methamphetamine and HIV-1 gsp120 through the P13K/Akt Pathway Induces IL-6 but not IL-8 Expression in Astrocytes

Dementia Associated with the Acquired Immunodeficiency Syndrome

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

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