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Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells

We recently reported that arsenic disrupted neuronal insulin signaling. Here, we further investigated the effect of arsenic on insulin receptor substrate (IRS) proteins, which are crucial downstream signaling molecules of insulin in differentiated human neuroblastoma SH-SY5Y cells. We also found tha...

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Autores principales: Wisessaowapak, Churaibhon, Weeraphan, Churat, Visitnonthachai, Daranee, Chokchaichamnankit, Daranee, Srisomsap, Chantragan, Watcharasit, Piyajit, Svasti, Jisnuson, Satayavivad, Jutamaad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010979/
https://www.ncbi.nlm.nih.gov/pubmed/36925548
http://dx.doi.org/10.1016/j.heliyon.2023.e14385
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author Wisessaowapak, Churaibhon
Weeraphan, Churat
Visitnonthachai, Daranee
Chokchaichamnankit, Daranee
Srisomsap, Chantragan
Watcharasit, Piyajit
Svasti, Jisnuson
Satayavivad, Jutamaad
author_facet Wisessaowapak, Churaibhon
Weeraphan, Churat
Visitnonthachai, Daranee
Chokchaichamnankit, Daranee
Srisomsap, Chantragan
Watcharasit, Piyajit
Svasti, Jisnuson
Satayavivad, Jutamaad
author_sort Wisessaowapak, Churaibhon
collection PubMed
description We recently reported that arsenic disrupted neuronal insulin signaling. Here, we further investigated the effect of arsenic on insulin receptor substrate (IRS) proteins, which are crucial downstream signaling molecules of insulin in differentiated human neuroblastoma SH-SY5Y cells. We also found that prolonged arsenic treatment accelerated the migration of IRS1 and IRS2 on SDS-PAGE. Treatment with phosphatases abolished the arsenic-induced increased mobility of IRS, suggesting that the electrophoretic mobility shift of IRS on SDS-PAGE by arsenic was phosphorylation-dependent. By using label-free mass spectrometry, the phosphorylation sites of IRS1 were found to be S24, S345, S636, T774, S1057, S1058, and S1070, while those of IRS2 were at S645, Y653, T657, S665, S667, S669, S672, S915, and S1203, which were at least 2-fold lower than found in the control. These findings indicated a global hypophosphorylation of IRS proteins after prolonged arsenic treatment. In addition, four novel phosphorylation sites were identified on IRS1 (T774, S1057, S1058, and S1070), with another two on IRS2 (S665 and S667). As basal IRS phosphorylation plays an important role in insulin signaling, the reduction of IRS phosphorylation on multiple residues may underlie arsenic-impaired insulin signaling in neurons.
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spelling pubmed-100109792023-03-15 Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells Wisessaowapak, Churaibhon Weeraphan, Churat Visitnonthachai, Daranee Chokchaichamnankit, Daranee Srisomsap, Chantragan Watcharasit, Piyajit Svasti, Jisnuson Satayavivad, Jutamaad Heliyon Research Article We recently reported that arsenic disrupted neuronal insulin signaling. Here, we further investigated the effect of arsenic on insulin receptor substrate (IRS) proteins, which are crucial downstream signaling molecules of insulin in differentiated human neuroblastoma SH-SY5Y cells. We also found that prolonged arsenic treatment accelerated the migration of IRS1 and IRS2 on SDS-PAGE. Treatment with phosphatases abolished the arsenic-induced increased mobility of IRS, suggesting that the electrophoretic mobility shift of IRS on SDS-PAGE by arsenic was phosphorylation-dependent. By using label-free mass spectrometry, the phosphorylation sites of IRS1 were found to be S24, S345, S636, T774, S1057, S1058, and S1070, while those of IRS2 were at S645, Y653, T657, S665, S667, S669, S672, S915, and S1203, which were at least 2-fold lower than found in the control. These findings indicated a global hypophosphorylation of IRS proteins after prolonged arsenic treatment. In addition, four novel phosphorylation sites were identified on IRS1 (T774, S1057, S1058, and S1070), with another two on IRS2 (S665 and S667). As basal IRS phosphorylation plays an important role in insulin signaling, the reduction of IRS phosphorylation on multiple residues may underlie arsenic-impaired insulin signaling in neurons. Elsevier 2023-03-08 /pmc/articles/PMC10010979/ /pubmed/36925548 http://dx.doi.org/10.1016/j.heliyon.2023.e14385 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Wisessaowapak, Churaibhon
Weeraphan, Churat
Visitnonthachai, Daranee
Chokchaichamnankit, Daranee
Srisomsap, Chantragan
Watcharasit, Piyajit
Svasti, Jisnuson
Satayavivad, Jutamaad
Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title_full Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title_fullStr Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title_full_unstemmed Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title_short Arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma SH-SY5Y cells
title_sort arsenic induces the global hypophosphorylation of insulin receptor substrate proteins in differentiated human neuroblastoma sh-sy5y cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010979/
https://www.ncbi.nlm.nih.gov/pubmed/36925548
http://dx.doi.org/10.1016/j.heliyon.2023.e14385
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