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Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Immunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumul...

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Autores principales: Mytych, Jennifer, Sołek, Przemysław, Będzińska, Agnieszka, Rusinek, Kinga, Warzybok, Aleksandra, Tabęcka-Łonczyńska, Anna, Koziorowski, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072557/
https://www.ncbi.nlm.nih.gov/pubmed/31972978
http://dx.doi.org/10.3390/cells9020261
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author Mytych, Jennifer
Sołek, Przemysław
Będzińska, Agnieszka
Rusinek, Kinga
Warzybok, Aleksandra
Tabęcka-Łonczyńska, Anna
Koziorowski, Marek
author_facet Mytych, Jennifer
Sołek, Przemysław
Będzińska, Agnieszka
Rusinek, Kinga
Warzybok, Aleksandra
Tabęcka-Łonczyńska, Anna
Koziorowski, Marek
author_sort Mytych, Jennifer
collection PubMed
description Immunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumulating DNA damage. However, some literature data suggest that endoplasmic reticulum and Golgi stress pathways may be involved in SASP development. Thus, the aim of this study was to investigate the role of klotho protein in the regulation of immunosenescence-associated Golgi apparatus and ER stress response induced by bacterial antigens in monocytes. We provide evidence that initiation of immunosenescent-like phenotype in monocytes is accompanied by activation of CREB34L and TFE3 Golgi stress response and ATF6 and IRE1 endoplasmic reticulum stress response, while klotho overexpression prevents these changes. Further, these changes are followed by upregulated secretion of proinflammatory cytokines, which final modification takes place exclusively in the Golgi apparatus. In conclusion, we provide for the first time evidence of klotho involvement in the crosstalk on the line ER-Golgi, which may, in turn, affect activation of SASP. This data may be useful for a novel potential target for therapy in age-related and chronic inflammatory conditions.
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spelling pubmed-70725572020-03-19 Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes Mytych, Jennifer Sołek, Przemysław Będzińska, Agnieszka Rusinek, Kinga Warzybok, Aleksandra Tabęcka-Łonczyńska, Anna Koziorowski, Marek Cells Article Immunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumulating DNA damage. However, some literature data suggest that endoplasmic reticulum and Golgi stress pathways may be involved in SASP development. Thus, the aim of this study was to investigate the role of klotho protein in the regulation of immunosenescence-associated Golgi apparatus and ER stress response induced by bacterial antigens in monocytes. We provide evidence that initiation of immunosenescent-like phenotype in monocytes is accompanied by activation of CREB34L and TFE3 Golgi stress response and ATF6 and IRE1 endoplasmic reticulum stress response, while klotho overexpression prevents these changes. Further, these changes are followed by upregulated secretion of proinflammatory cytokines, which final modification takes place exclusively in the Golgi apparatus. In conclusion, we provide for the first time evidence of klotho involvement in the crosstalk on the line ER-Golgi, which may, in turn, affect activation of SASP. This data may be useful for a novel potential target for therapy in age-related and chronic inflammatory conditions. MDPI 2020-01-21 /pmc/articles/PMC7072557/ /pubmed/31972978 http://dx.doi.org/10.3390/cells9020261 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mytych, Jennifer
Sołek, Przemysław
Będzińska, Agnieszka
Rusinek, Kinga
Warzybok, Aleksandra
Tabęcka-Łonczyńska, Anna
Koziorowski, Marek
Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title_full Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title_fullStr Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title_full_unstemmed Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title_short Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
title_sort towards age-related anti-inflammatory therapy: klotho suppresses activation of er and golgi stress response in senescent monocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072557/
https://www.ncbi.nlm.nih.gov/pubmed/31972978
http://dx.doi.org/10.3390/cells9020261
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