The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons
<div><p>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 exci...
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| مؤلفون آخرون: | , , , |
| منشور في: |
2019
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| _version_ | 1864513520283942912 |
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| author | Wesal Habbab (17346961) |
| author2 | Imad Aoudé (18174946) Freshteh Palangi (4278685) Sara Abdulla (8548053) Tariq Ahmed (5768081) |
| author2_role | author author author author |
| author_facet | Wesal Habbab (17346961) Imad Aoudé (18174946) Freshteh Palangi (4278685) Sara Abdulla (8548053) Tariq Ahmed (5768081) |
| author_role | author |
| dc.creator.none.fl_str_mv | Wesal Habbab (17346961) Imad Aoudé (18174946) Freshteh Palangi (4278685) Sara Abdulla (8548053) Tariq Ahmed (5768081) |
| dc.date.none.fl_str_mv | 2019-02-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ijms20040844 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_Anti-Tumor_Agent_Sodium_Selenate_Decreases_Methylated_PP2A_Increases_GSK3_Y216_Phosphorylation_Including_Tau_Disease_Epitopes_and_Reduces_Neuronal_Excitability_in_SHSY-5Y_Neurons/25428316 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Chemical sciences Analytical chemistry Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry PP2A GSK3β Tau retinoic acid differentiated SHSY-5Y cells |
| dc.title.none.fl_str_mv | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms20040844" target="_blank">https://dx.doi.org/10.3390/ijms20040844</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_28eac97404c76133318dcf8eb1b7ecb5 |
| identifier_str_mv | 10.3390/ijms20040844 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25428316 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y NeuronsWesal Habbab (17346961)Imad Aoudé (18174946)Freshteh Palangi (4278685)Sara Abdulla (8548053)Tariq Ahmed (5768081)Chemical sciencesAnalytical chemistryInorganic chemistryOrganic chemistryPhysical chemistryTheoretical and computational chemistryPP2AGSK3βTauretinoic acid differentiated SHSY-5Y cells<div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms20040844" target="_blank">https://dx.doi.org/10.3390/ijms20040844</a></p>2019-02-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms20040844https://figshare.com/articles/journal_contribution/The_Anti-Tumor_Agent_Sodium_Selenate_Decreases_Methylated_PP2A_Increases_GSK3_Y216_Phosphorylation_Including_Tau_Disease_Epitopes_and_Reduces_Neuronal_Excitability_in_SHSY-5Y_Neurons/25428316CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/254283162019-02-15T03:00:00Z |
| spellingShingle | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons Wesal Habbab (17346961) Chemical sciences Analytical chemistry Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry PP2A GSK3β Tau retinoic acid differentiated SHSY-5Y cells |
| status_str | publishedVersion |
| title | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| title_full | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| title_fullStr | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| title_full_unstemmed | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| title_short | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| title_sort | The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3βY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons |
| topic | Chemical sciences Analytical chemistry Inorganic chemistry Organic chemistry Physical chemistry Theoretical and computational chemistry PP2A GSK3β Tau retinoic acid differentiated SHSY-5Y cells |