Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease

Increased amyloid-beta (Aβ) and amyloid precursor protein (APP) in the brains of Alzheimer’s disease (AD) patients are common pathological hallmarks mediating the disease progression. Growing evidence also suggests that mitochondrial abnormalities are an early feature in the pathogenesis of AD. Inte...

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Autores principales:	Aslina Pahrudin Arrozi, Wan Zurinah Wan Ngah, Hanafi Ahmad Damanhuri, Suzana Makpol
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tocopherol amyloid precursor proteins respiratory capacity membrane potential Alzheimer’s disease Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9db1ebba1c744ebdad308529e21ba89b
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spelling	oai:doaj.org-article:9db1ebba1c744ebdad308529e21ba89b2021-11-22T07:30:05ZModulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease1663-981210.3389/fphar.2021.698833https://doaj.org/article/9db1ebba1c744ebdad308529e21ba89b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.698833/fullhttps://doaj.org/toc/1663-9812Increased amyloid-beta (Aβ) and amyloid precursor protein (APP) in the brains of Alzheimer’s disease (AD) patients are common pathological hallmarks mediating the disease progression. Growing evidence also suggests that mitochondrial abnormalities are an early feature in the pathogenesis of AD. Intervention with antioxidants has received great interest as a molecular strategy for the manipulation of mitochondrial function. Our previous preliminary study using in vitro cell models expressing different types of APP demonstrated that treatment with alpha-tocopherol (ATF) or gamma-tocopherol (GTF) modulates mitochondrial function by reducing mitochondrial reactive oxygen species (ROS), increasing the production of ATP and preventing apoptosis events, especially in cells expressing the mutant APP form. Thus, we hypothesized that ATF or GTF treatment might also alter mitochondrial metabolic pathways such as oxidative phosphorylation. The present study aimed to investigate the role of ATF and GTF in modulating mitochondrial oxidative metabolism using high-resolution respirometry. Our results showed that both ATF and GTF increased the respiratory capacity and membrane potential in the ROUTINE and OXPHOSCI-LINKED states as well as complex IV enzyme activity in wild-type and mutant APP-overexpressing SH-SY5Y cells. Although preliminary, these findings indicate that ATF and GTF modulate mitochondrial oxidative metabolism in APP-overexpressing cells and, in part, may contribute to the planning of strategies for utilizing vitamin E isomers against mitochondrial-related diseases such as AD.Aslina Pahrudin ArroziWan Zurinah Wan NgahHanafi Ahmad DamanhuriSuzana MakpolFrontiers Media S.A.articletocopherolamyloid precursor proteinsrespiratory capacitymembrane potentialAlzheimer’s diseaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tocopherol amyloid precursor proteins respiratory capacity membrane potential Alzheimer’s disease Therapeutics. Pharmacology RM1-950
spellingShingle	tocopherol amyloid precursor proteins respiratory capacity membrane potential Alzheimer’s disease Therapeutics. Pharmacology RM1-950 Aslina Pahrudin Arrozi Wan Zurinah Wan Ngah Hanafi Ahmad Damanhuri Suzana Makpol Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
description	Increased amyloid-beta (Aβ) and amyloid precursor protein (APP) in the brains of Alzheimer’s disease (AD) patients are common pathological hallmarks mediating the disease progression. Growing evidence also suggests that mitochondrial abnormalities are an early feature in the pathogenesis of AD. Intervention with antioxidants has received great interest as a molecular strategy for the manipulation of mitochondrial function. Our previous preliminary study using in vitro cell models expressing different types of APP demonstrated that treatment with alpha-tocopherol (ATF) or gamma-tocopherol (GTF) modulates mitochondrial function by reducing mitochondrial reactive oxygen species (ROS), increasing the production of ATP and preventing apoptosis events, especially in cells expressing the mutant APP form. Thus, we hypothesized that ATF or GTF treatment might also alter mitochondrial metabolic pathways such as oxidative phosphorylation. The present study aimed to investigate the role of ATF and GTF in modulating mitochondrial oxidative metabolism using high-resolution respirometry. Our results showed that both ATF and GTF increased the respiratory capacity and membrane potential in the ROUTINE and OXPHOSCI-LINKED states as well as complex IV enzyme activity in wild-type and mutant APP-overexpressing SH-SY5Y cells. Although preliminary, these findings indicate that ATF and GTF modulate mitochondrial oxidative metabolism in APP-overexpressing cells and, in part, may contribute to the planning of strategies for utilizing vitamin E isomers against mitochondrial-related diseases such as AD.
format	article
author	Aslina Pahrudin Arrozi Wan Zurinah Wan Ngah Hanafi Ahmad Damanhuri Suzana Makpol
author_facet	Aslina Pahrudin Arrozi Wan Zurinah Wan Ngah Hanafi Ahmad Damanhuri Suzana Makpol
author_sort	Aslina Pahrudin Arrozi
title	Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
title_short	Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
title_full	Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
title_fullStr	Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
title_full_unstemmed	Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
title_sort	modulatory effects of alpha- and gamma-tocopherol on the mitochondrial respiratory capacity and membrane potential in an in vitro model of alzheimer’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9db1ebba1c744ebdad308529e21ba89b
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Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease

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