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Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signa...

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Autores principales: Paunovic, Verica, Peric, Stojan, Vukovic, Irena, Stamenkovic, Marina, Milosevic, Emina, Stevanovic, Danijela, Mandic, Milos, Basta, Ivana, Berisavac, Ivana, Arsenijevic, Mirjana, Bozovic, Ivo, Nikolic, Marko, Stevic, Zorica, Trajkovic, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496801/
https://www.ncbi.nlm.nih.gov/pubmed/36139470
http://dx.doi.org/10.3390/cells11182897
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author Paunovic, Verica
Peric, Stojan
Vukovic, Irena
Stamenkovic, Marina
Milosevic, Emina
Stevanovic, Danijela
Mandic, Milos
Basta, Ivana
Berisavac, Ivana
Arsenijevic, Mirjana
Bozovic, Ivo
Nikolic, Marko
Stevic, Zorica
Trajkovic, Vladimir
author_facet Paunovic, Verica
Peric, Stojan
Vukovic, Irena
Stamenkovic, Marina
Milosevic, Emina
Stevanovic, Danijela
Mandic, Milos
Basta, Ivana
Berisavac, Ivana
Arsenijevic, Mirjana
Bozovic, Ivo
Nikolic, Marko
Stevic, Zorica
Trajkovic, Vladimir
author_sort Paunovic, Verica
collection PubMed
description AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.
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spelling pubmed-94968012022-09-23 Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome Paunovic, Verica Peric, Stojan Vukovic, Irena Stamenkovic, Marina Milosevic, Emina Stevanovic, Danijela Mandic, Milos Basta, Ivana Berisavac, Ivana Arsenijevic, Mirjana Bozovic, Ivo Nikolic, Marko Stevic, Zorica Trajkovic, Vladimir Cells Article AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy. MDPI 2022-09-16 /pmc/articles/PMC9496801/ /pubmed/36139470 http://dx.doi.org/10.3390/cells11182897 Text en © 2022 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 Article
Paunovic, Verica
Peric, Stojan
Vukovic, Irena
Stamenkovic, Marina
Milosevic, Emina
Stevanovic, Danijela
Mandic, Milos
Basta, Ivana
Berisavac, Ivana
Arsenijevic, Mirjana
Bozovic, Ivo
Nikolic, Marko
Stevic, Zorica
Trajkovic, Vladimir
Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title_full Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title_fullStr Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title_full_unstemmed Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title_short Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
title_sort downregulation of lkb1/ampk signaling in blood mononuclear cells is associated with the severity of guillain–barre syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496801/
https://www.ncbi.nlm.nih.gov/pubmed/36139470
http://dx.doi.org/10.3390/cells11182897
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