Sodium tungstate (Na<sub>2</sub>WO<sub>4</sub>) exposure increases apoptosis in human peripheral blood lymphocytes

Osterburg, Andrew R.; Robinson, Chad T.; Schwemberger, Sandy; Mokashi, Vishwesh; Stockelman, Michael; Babcock, George F.

doi:10.3109/15476911003631617

Cited by 36 publications

(36 citation statements)

References 34 publications

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“…For instance, microtubule disorganization occurs in self-incompatibility-mediated PCD of Papaver rhoeas pollen (Bosch et al 2008;Poulter et al 2008). Recently, it has been reported that exposure to W is correlated with apoptosis in human blood lymphocytes (Osterburg et al 2010). Taking into account these data from pea, as well as the above report from human cells, we examined the possibility that W toxicity to pea roots may be associated with some type of PCD.…”

Section: Introductionmentioning

confidence: 99%

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

Adamakis

Panteris

Eleftheriou

2011

Planta

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Programmed cell death (PCD) is a widespread response of plants against abiotic stress, such as heavy metal toxicity. Tungsten (W) is increasingly considered toxic for plants since it irreversibly affects their growth. Therefore, we investigated whether W could induce some kind of PCD in plants, like other heavy metals do. The morphology of cell and nucleus, the integrity of the cytoskeleton, Evans Blue absorbance and the expression of PCD-related genes were used as indicators of PCD in W-treated roots of Pisum sativum (pea). TEM and fluorescence microscopy revealed mitotic cycle arrest, protoplast shrinkage, disruption of the cytoskeleton and chromatin condensation and peripheral distribution in the nucleus of W-affected cells. Moreover, Evans Blue absorbance in roots increased in relation to the duration of W treatment. These effects were suppressed by inhibitors of the 26S proteasome, caspases and endoplasmic reticulum stress. In addition, silencing of DAD-1 and induction of HSR203J, BiP-D, bZIP28 and bZIP60 genes were also recorded in W-treated pea roots by semi-quantitative RT-PCR. The above observations show that W induces a kind of PCD in pea roots, further substantiating its toxicity for plants. Data imply that endoplasmic reticulum stress-unfolded protein response may be involved in W-induced PCD.

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Section: Introductionmentioning

confidence: 99%

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

Adamakis

Panteris

Eleftheriou

2011

Planta

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“…Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models (Osterburg et al, 2010, 2014; Fastje et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

“…Disruption of redox processes leads to altered expression of FasL and Bcl2 in T-cells (Yang et al, 2013), and inhibition of CD8 + T-cell proliferation and function (Sklavos et al, 2008). Tungstate exposure has been associated with increased apoptosis in vitro in human and murine leukocytes (Osterburg et al, 2010; Guilbert et al, 2011); with DNA damage in vivo in bone marrow cells in C57BL/6J mice (Guilbert et al, 2011); with activation of antioxidant enzymes (Nakhaee et al, 2010; Donmez et al, 2014); and with up-regulation of pro-apoptotic genes (Lombaert et al, 2008; Harris et al, 2015) and proteins (Zhao et al, 2013) in rats and human and rodent cultured cells. However, in the present study, no increases in apoptosis, tingible body macrophages, or cell loss were evident in groups administered STD compared to control groups when hosts were evaluated using enhanced histopathology or spleen cell immunophenotyping.…”

Section: Discussionmentioning

confidence: 99%

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Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Frawley

Smith

White

et al. 2016

Journal of Immunotoxicology

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Tungsten is a naturally occurring, high tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0–2000 mg STD/L in their drinking water for 28 days, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3+ T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely effect cell-mediated immunity.

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“…Our studies compliment findings by Osterburg et al, which investigated the effect of Na 2 WO 4 on human peripheral blood lymphocytes in vitro. They demonstrated that at 1 mM dose, significant toxicity occurred, while 0.01 and 0.1 mM Na 2 WO 4 did not stimulate an immune response [47]. Na 2 WO 4 as a water soluble small molecule could be readily delivered to sites of injury through direct injection or incorporated in drug delivery or scaffolding devices.…”

Section: Figmentioning

confidence: 99%

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

Khader

Sherman

Rameshwar

et al. 2016

Stem Cells and Development

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Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na 2 WO 4 ), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin. Na 2 WO 4 was added to the media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic differentiation was assessed by biochemical analyses, immunostaining, and gene expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS) was also investigated. The chondrogenic differentiation of MSCs was enhanced in the presence of low concentrations of Na 2 WO 4 compared to control, without Na 2 WO 4 . In the induction medium containing insulin, cells in 0.01 mM Na 2 WO 4 produced significantly higher sulfated glycosaminoglycans, collagen type II, and chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM Na 2 WO 4 had significantly higher collagen II production and significantly higher sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and induction medium without insulin containing low concentrations of Na 2 WO 4 also expressed chondrogenic markers. Na 2 WO 4 did not stimulate PBMC proliferation or apoptosis. The results demonstrate that Na 2 WO 4 enhances chondrogenic differentiation of MSCs, does not have a toxic effect, and may be useful for MSC-based approaches for cartilage repair.

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Sodium tungstate (Na₂WO₄) exposure increases apoptosis in human peripheral blood lymphocytes

Cited by 36 publications

References 34 publications

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

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Sodium tungstate (Na2WO4) exposure increases apoptosis in human peripheral blood lymphocytes

Cited by 36 publications

References 34 publications

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

The fatal effect of tungsten on Pisum sativum L. root cells: indications for endoplasmic reticulum stress-induced programmed cell death

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

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Sodium tungstate (Na₂WO₄) exposure increases apoptosis in human peripheral blood lymphocytes

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water