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Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells

The beta-cell identity gene, pancreatic duodenal homeobox 1 (Pdx1), plays critical roles in many aspects of the life of beta-cells including differentiation, maturation, function, survival and proliferation. High levels of reactive oxygen species (ROS) are extremely toxic to cells and especially to...

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Autores principales: Baumel-Alterzon, Sharon, Scott, Donald K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521308/
https://www.ncbi.nlm.nih.gov/pubmed/36187092
http://dx.doi.org/10.3389/fendo.2022.1011187
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author Baumel-Alterzon, Sharon
Scott, Donald K.
author_facet Baumel-Alterzon, Sharon
Scott, Donald K.
author_sort Baumel-Alterzon, Sharon
collection PubMed
description The beta-cell identity gene, pancreatic duodenal homeobox 1 (Pdx1), plays critical roles in many aspects of the life of beta-cells including differentiation, maturation, function, survival and proliferation. High levels of reactive oxygen species (ROS) are extremely toxic to cells and especially to beta-cells due to their relatively low expression of antioxidant enzymes. One of the major mechanisms for beta-cell dysfunction in type-2 diabetes results from oxidative stress-dependent inhibition of PDX1 levels and function. ROS inhibits Pdx1 by reducing Pdx1 mRNA and protein levels, inhibiting PDX1 nuclear localization, and suppressing PDX1 coactivator complexes. The nuclear factor erythroid 2-related factor (Nrf2) antioxidant pathway controls the redox balance and allows the maintenance of high Pdx1 levels. Therefore, pharmacological activation of the Nrf2 pathway may alleviate diabetes by preserving Pdx1 levels.
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spelling pubmed-95213082022-09-30 Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells Baumel-Alterzon, Sharon Scott, Donald K. Front Endocrinol (Lausanne) Endocrinology The beta-cell identity gene, pancreatic duodenal homeobox 1 (Pdx1), plays critical roles in many aspects of the life of beta-cells including differentiation, maturation, function, survival and proliferation. High levels of reactive oxygen species (ROS) are extremely toxic to cells and especially to beta-cells due to their relatively low expression of antioxidant enzymes. One of the major mechanisms for beta-cell dysfunction in type-2 diabetes results from oxidative stress-dependent inhibition of PDX1 levels and function. ROS inhibits Pdx1 by reducing Pdx1 mRNA and protein levels, inhibiting PDX1 nuclear localization, and suppressing PDX1 coactivator complexes. The nuclear factor erythroid 2-related factor (Nrf2) antioxidant pathway controls the redox balance and allows the maintenance of high Pdx1 levels. Therefore, pharmacological activation of the Nrf2 pathway may alleviate diabetes by preserving Pdx1 levels. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9521308/ /pubmed/36187092 http://dx.doi.org/10.3389/fendo.2022.1011187 Text en Copyright © 2022 Baumel-Alterzon and Scott https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Baumel-Alterzon, Sharon
Scott, Donald K.
Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title_full Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title_fullStr Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title_full_unstemmed Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title_short Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells
title_sort regulation of pdx1 by oxidative stress and nrf2 in pancreatic beta-cells
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521308/
https://www.ncbi.nlm.nih.gov/pubmed/36187092
http://dx.doi.org/10.3389/fendo.2022.1011187
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