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Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts
The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative stress in pig...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773735/ https://www.ncbi.nlm.nih.gov/pubmed/35052845 http://dx.doi.org/10.3390/biomedicines10010165 |
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author | Tian, Liang Liu, Guangfan Kang, Ziqi Yan, Peishi |
author_facet | Tian, Liang Liu, Guangfan Kang, Ziqi Yan, Peishi |
author_sort | Tian, Liang |
collection | PubMed |
description | The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative stress in pig trophoblasts, as evidenced by decreased total antioxidant capacity (TAC); higher production of reactive oxygen species (ROS); elevated protein carbonylation; and reduced SOD, CAT, and GSH-PX activities. Further analyses revealed MARK4 impaired mitochondrial oxidative respiration in cultured trophoblasts, which was associated with reduced ATP content, decreased mitochondrial membrane potential, lower mitochondrial Complexes I and III activities, and down-regulated protein contents of subunits of complexes I, II, and V. At same time, mitochondrial biogenesis and structure were negatively altered by elevated MARK4. By antioxidant treatment with vitamin E (VE), oxidative stress along with impaired mitochondrial function induced by enhanced MARK4 were blocked. Furthermore, we found activation of AMPK signaling prevented MARK4 from blocking mitochondrial biogenesis and function in pig trophoblast cells. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in MARK4 activated oxidative stress and mitochondrial dysfunction. Thus, these data suggest that MARK4 promotes oxidative stress and mitochondrial injury in porcine placental trophoblasts and can contribute to the developing of knowledge of pathological processes leading to mitochondrial dysfunction associated with excessive back-fat in the pig placenta and to the obesity-associated pregnant syndrome. |
format | Online Article Text |
id | pubmed-8773735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87737352022-01-21 Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts Tian, Liang Liu, Guangfan Kang, Ziqi Yan, Peishi Biomedicines Article The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative stress in pig trophoblasts, as evidenced by decreased total antioxidant capacity (TAC); higher production of reactive oxygen species (ROS); elevated protein carbonylation; and reduced SOD, CAT, and GSH-PX activities. Further analyses revealed MARK4 impaired mitochondrial oxidative respiration in cultured trophoblasts, which was associated with reduced ATP content, decreased mitochondrial membrane potential, lower mitochondrial Complexes I and III activities, and down-regulated protein contents of subunits of complexes I, II, and V. At same time, mitochondrial biogenesis and structure were negatively altered by elevated MARK4. By antioxidant treatment with vitamin E (VE), oxidative stress along with impaired mitochondrial function induced by enhanced MARK4 were blocked. Furthermore, we found activation of AMPK signaling prevented MARK4 from blocking mitochondrial biogenesis and function in pig trophoblast cells. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in MARK4 activated oxidative stress and mitochondrial dysfunction. Thus, these data suggest that MARK4 promotes oxidative stress and mitochondrial injury in porcine placental trophoblasts and can contribute to the developing of knowledge of pathological processes leading to mitochondrial dysfunction associated with excessive back-fat in the pig placenta and to the obesity-associated pregnant syndrome. MDPI 2022-01-13 /pmc/articles/PMC8773735/ /pubmed/35052845 http://dx.doi.org/10.3390/biomedicines10010165 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 Tian, Liang Liu, Guangfan Kang, Ziqi Yan, Peishi Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title | Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title_full | Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title_fullStr | Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title_full_unstemmed | Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title_short | Microtubule Affinity-Regulating Kinase 4 Promotes Oxidative Stress and Mitochondrial Dysfunction by Activating NF-κB and Inhibiting AMPK Pathways in Porcine Placental Trophoblasts |
title_sort | microtubule affinity-regulating kinase 4 promotes oxidative stress and mitochondrial dysfunction by activating nf-κb and inhibiting ampk pathways in porcine placental trophoblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773735/ https://www.ncbi.nlm.nih.gov/pubmed/35052845 http://dx.doi.org/10.3390/biomedicines10010165 |
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