Dataset Information

The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons.

ABSTRACT: Selenium application as sodium selenate was repeatedly shown to have anti-carcinogenic properties by increasing levels of the serine/ threonine protein phosphatase 2A (PP2A) in cancer cells. PP2A has a prominent role in cell development, homeostasis, and in neurons regulates excitability. PP2A, GSK3β and Tau reside together in a complex, which facilitates their interaction and (dys)-function as has been reported for several neurological disorders. In this study we recorded maximum increase in total PP2A at 3 µM sodium selenate in a neuron cell line. In conjunction with these data, whole-cell electrophysiological studies revealed that this concentration had maximum effect on membrane potentials, conductance and currents. Somewhat surprisingly, the catalytically active form, methylated PP2A (mePP2A) was significantly decreased. In close correlation to these data, the phosphorylation state of two substrate proteins, sensitive to PP2A activity, GSK3β and Tau were found to be increased. In summary, our data reveal that sodium selenate enhances PP2A levels, but reduces catalytic activity of PP2A in a dose dependent manner, which fails to reduce Tau and GSK3β phosphorylation under physiological conditions, indicating an alternative route in the rescue of cell pathology in neurological disorders.

SUBMITTER: Habbab W

PROVIDER: S-EPMC6412488 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons.

Habbab Wesal W Aoudé Imad I Palangi Freshteh F Abdulla Sara S Ahmed Tariq T

International journal of molecular sciences 20190215 4

Selenium application as sodium selenate was repeatedly shown to have anti-carcinogenic properties by increasing levels of the serine/ threonine protein phosphatase 2A (PP2A) in cancer cells. PP2A has a prominent role in cell development, homeostasis, and in neurons regulates excitability. PP2A, GSK3β and Tau reside together in a complex, which facilitates their interaction and (dys)-function as has been reported for several neurological disorders. In this study we recorded maximum increase in to ...[more]

PMID: 30781361

Similar Datasets

Project description:The modulation of the brain's electrical activity for therapeutic purposes has recently gained attention, supported by the promising results obtained through the non-invasive application of transcranial direct current stimulation (tDCS) in the treatment of neurodegenerative and neurological diseases. To optimize therapeutic efficacy, it is crucial to investigate the cellular and molecular effects of tDCS. This will help to identify important biomarkers, predict patient's response and develop personalized treatments. In this study, we applied direct current stimulation (DCS) to a neural cell line, using mild currents over short periods of time (0.5 mA, 20 min), with 24-h intervals. We observed that DCS induced changes in the cellular lipidome, with transient effects observed after a single stimulation (lasting 24 h) and more significant, long-lasting effects (up to 72 h) after repeated stimulation cycles. In neural cells, multiple DCS treatment modulated structural membrane lipids (PE, PS, PI), downregulated glycerol lipids with ether-linked fatty acids and pro-inflammatory lipids (ceramides and lyso-glycerophospholipids) (p ≤ 0.005). Multiple DCS sessions altered transcriptional activity by decreasing the expression of inflammatory cytokines (TNF-α, p ≤ 0.05; IL-1β, p ≤ 0.01), while increasing the expression of neuroprotective factors such as heme oxygenase-1 (p ≤ 0.0001) and brain-derived neurotrophic factor (p ≤ 0.05), as well as proteins involved in vesicular transport (SNARE, sorting nexins and seipin and α-synuclein; p ≤ 0.05). In addition, DCS enhanced the release of extracellular vesicles, with repeated stimulations significantly increasing the release of exosomes threefold. In conclusion, while a single electrical stimulation induces transient metabolic changes with limited phenotypic effects, repeated applications induce a broader and deeper modulation of lipid species. This may lead to a neuroprotective and neuroplasticity-focussed transcriptional profile, potentially supporting the therapeutic effects of tDCS at the cellular and molecular level in patients..

Project description:Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage. Therefore, the purpose of this study was to determine whether one such agent, melatonin (Mel), could confer protection against Oxa-induced neurotoxicity in SH-SY5Y cells. Results from the present study found Oxa to significantly reduce SH-SY5Y cell viability in a dose-dependent manner. Alternatively, we found Mel pre-treatment to SH-SY5Y cells to attenuate Oxa-induced toxicity, resulting in a markedly increased cell viability. Mel exerted its protective effects by regulating reactive oxygen species (ROS) production and reducing superoxide radicals inside Oxa-exposed. In addition, we observed pre-treatment with Mel to rescue Oxa-treated cells by protecting mitochondria. As Oxa-treatment alone decreases mitochondrial membrane potential (Δψm), resulting in an altered Bcl-2/Bax ratio and release of sequestered cytochrome c, so Mel was shown to inhibit these pathways. Mel was also found to inhibit proteolytic activation of caspase 3, inactivation of Poly (ADP Ribose) polymerase, and DNA damage, thereby allowing SH-SY5Y cells to resist apoptotic cell death. Collectively, our results suggest a role for melatonin in reducing Oxa induced neurotoxicity. Further studies exploring melatonin's protective effects may prove successful in eliciting pathways to further alter the neurotoxic pathways of platinum compounds in cancer treatment.

Dataset Information

The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons.

Publications

The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets