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Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK

The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative st...

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Autores principales: Hurtado-Carneiro, Verónica, Dongil, Pilar, Pérez-García, Ana, Álvarez, Elvira, Sanz, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698360/
https://www.ncbi.nlm.nih.gov/pubmed/34943132
http://dx.doi.org/10.3390/antiox10122028
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author Hurtado-Carneiro, Verónica
Dongil, Pilar
Pérez-García, Ana
Álvarez, Elvira
Sanz, Carmen
author_facet Hurtado-Carneiro, Verónica
Dongil, Pilar
Pérez-García, Ana
Álvarez, Elvira
Sanz, Carmen
author_sort Hurtado-Carneiro, Verónica
collection PubMed
description The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.
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spelling pubmed-86983602021-12-24 Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK Hurtado-Carneiro, Verónica Dongil, Pilar Pérez-García, Ana Álvarez, Elvira Sanz, Carmen Antioxidants (Basel) Review The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress. MDPI 2021-12-20 /pmc/articles/PMC8698360/ /pubmed/34943132 http://dx.doi.org/10.3390/antiox10122028 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hurtado-Carneiro, Verónica
Dongil, Pilar
Pérez-García, Ana
Álvarez, Elvira
Sanz, Carmen
Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title_full Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title_fullStr Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title_full_unstemmed Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title_short Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK
title_sort preventing oxidative stress in the liver: an opportunity for glp-1 and/or pask
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698360/
https://www.ncbi.nlm.nih.gov/pubmed/34943132
http://dx.doi.org/10.3390/antiox10122028
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