The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

Scofield, Virginia L.; Yan, Ming; Kuang, Xi; Kim, Soo Jin; Wong, Patty

doi:10.1016/j.imlet.2008.12.012

Cited by 14 publications

(24 citation statements)

References 51 publications

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“…Activation and stabilization of Nrf2 has previously been shown to be a protective mechanism adapted by the endothelial cells against ROS/NOS induced by sheer stress (Warabi et al, 2007) as well as in cadmium-induced oxidative stress (He et al, 2008). We have shown recently that GVT prevents ts 1-induced damage in T cells in the thymus, and in intestinal T cells, by upregulating and stabilizing Nrf2 levels in these cells (Scofield et al, 2009a; Scofield et al, 2009b). In infected T cells, GVT-induced restoration of redox equilibrium prevents gPr80 env accumulation, which we know to be the primary trigger for ts 1-induced cytopathology and cell death in astrocytes (Scofield et al, 2009a; Scofield et al, 2009b).…”

Section: Discussionmentioning

confidence: 99%

“…We have shown recently that GVT prevents ts 1-induced damage in T cells in the thymus, and in intestinal T cells, by upregulating and stabilizing Nrf2 levels in these cells (Scofield et al, 2009a; Scofield et al, 2009b). In infected T cells, GVT-induced restoration of redox equilibrium prevents gPr80 env accumulation, which we know to be the primary trigger for ts 1-induced cytopathology and cell death in astrocytes (Scofield et al, 2009a; Scofield et al, 2009b). …”

Section: Discussionmentioning

confidence: 99%

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Neuroprotective effects of the drug GVT (monosodium luminol) are mediated by the stabilization of Nrf2 in astrocytes

Reddy

Lungu

Kuang

et al. 2010

Neurochemistry International

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Oxidative stress is implicated in various kinds of neurological disorders, including human immunodeficiency virus (HIV) associated dementia (HAD). Our laboratory has been studying the murine retrovirus ts1, a pathogenic mutant of the Moloney murine leukemia virus (MoMuLV), as a model for HAD. Like HIV in humans, ts1 induces oxidative stress and progressive neurodegeneration in mice. We have shown previously that an antioxidant and anti-inflammatory drug GVT or MSL (monosodium luminol) suppresses ts1-induced oxidative stress, attenuates the development of spoorm encephalopathy, and delays hind limb paralysis in infected mice. It is known that upregulation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2) is involved in upregulating cellular antioxidant defenses. Since Nrf2 is associated with elevation of antioxidant defenses in general, and since GVT suppresses ts1-induced neurodegeneration, our aim in this study was to determine whether GVT neuroprotection is linked to Nrf2 upregulation in the brain. We report here that GVT upregulates the levels of Nrf2, both in primary astrocyte cultures and in brainstem of ts1-infected mice. Significant upregulation of Nrf2 expression by GVT occurs in both the cytosolic and nuclear fractions of cultured astrocytes and brainstem cells. Notably, although GVT treatment increases Nrf2 protein levels in cultured astrocytes and brainstem tissues, Nrf2 mRNA levels are not altered. This suggests that the neuroprotective effects of GVT may be mediated by the stabilization of the Nrf2 protein, allowing continuous upregulation of Nrf2 levels in the astrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of the drug GVT (monosodium luminol) are mediated by the stabilization of Nrf2 in astrocytes

Reddy

Lungu

Kuang

et al. 2010

Neurochemistry International

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“…IL6 and its family members23, and other molecules, e.g. reactive oxygen species24, signalling molecules25, and caspases26 play important roles during infection-induced thymic atrophy.…”

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confidence: 99%

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

Majumdar

Deobagkar-Lele

Adiga

et al. 2017

Sci Rep

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The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4−CD8− double negative (DN) thymocytes is observed. Second, CD4+CD8+ double positive (DP) thymocytes, mainly in the DP1 (CD5loCD3lo) and DP2 (CD5hiCD3int), but not DP3 (CD5intCD3hi), subsets are reduced. Third, single positive (SP) thymocytes are more resistant to depletion but their maturation is delayed, leading to accumulation of CD24hiCD3hi SP. Kinetic studies during infection demonstrated differences in sensitivity of thymic subpopulations: Immature single positive (ISP) > DP1, DP2 > DN3, DN4 > DN2 > CD4+ > CD8+. Upon infection, glucocorticoids (GC), inflammatory cytokines, e.g. Ifnγ, etc are induced, which enhance thymocyte death. Treatment with RU486, the GC receptor antagonist, increases the survival of most thymic subsets during infection. Studies with Ifnγ−/− mice demonstrated that endogenous Ifnγ produced during infection enhances the depletion of DN2-DN4 subsets, promotes the accumulation of DP3 and delays the maturation of SP thymocytes. The implications of these observations on host cellular responses during infections are discussed.

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“…The thymocytes and TECs survive infection, and gPr80 env does not accumulate in infected thymocytes. As for the intestine [97], our data suggest that this protection could occur either in two ways: via direct antioxidant activity by GVT, or lowering of thymocyte intracellular redox setpoints by gluthione (GSH) or by GSH precursors, both produced and provided to the thymocytes by TECs as a consequence of their upregulation of Nrf2.…”

Section: Discussionmentioning

confidence: 90%

“…The simplest way to interpret the systemic protective effect of GVT in ts1 infection, then, would start with the thymus. The survival and apparent homeostasis of its TEC and thymocyte cell compartments, under GVT treatment, could be the basis of what becomes either a fatal disease or a harmless infection in other tissues as well (including the intestine [97]). In the ts1-GVT thymus, we have shown here (1) that the TECs maintain normal characteristics in ts1-GVT mice; (2) that thymocytes of ts1-GVT mice survive despite continued infection; (3) that the thymocytes have lower than normal ROS levels; (4) that TEC Nrf2 levels are upregulated and stabilized; and (5) that these thymocytes do not contain accumulated gPr80 env .…”

Section: Discussionmentioning

confidence: 99%

The drug monosodium luminol (GVT®) preserves thymic epithelial cell cytoarchitecture and allows thymocyte survival in mice infected with the T cell-tropic, cytopathic retrovirus ts1

et al. 2009

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The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

Cited by 14 publications

References 51 publications

Neuroprotective effects of the drug GVT (monosodium luminol) are mediated by the stabilization of Nrf2 in astrocytes

Neuroprotective effects of the drug GVT (monosodium luminol) are mediated by the stabilization of Nrf2 in astrocytes

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

The drug monosodium luminol (GVT®) preserves thymic epithelial cell cytoarchitecture and allows thymocyte survival in mice infected with the T cell-tropic, cytopathic retrovirus ts1

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