Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line

Oxidative stress (OS) resulting from imbalance in the generation of reactive oxygen species (ROS) and/or the dysfunction of the antioxidant machinery, is a key mechanism associated with the onset of neurodegenerative disorders. Although the molecular mechanisms are still elusive, the onset of disord...

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Autores principales:	Lissette Sanchez-Aranguren, Mandeep Kaur Marwah, Sarah Nadeem
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Oxidative stress Neurodegenerative disorders Mitochondrial dysfunction Hydrogen sulphide donors Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/f4f1928fd69a4c29b4da17353b058355
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spelling	oai:doaj.org-article:f4f1928fd69a4c29b4da17353b0583552021-11-30T04:18:01ZNeuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line2667-137910.1016/j.arres.2021.100024https://doaj.org/article/f4f1928fd69a4c29b4da17353b0583552021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667137921000242https://doaj.org/toc/2667-1379Oxidative stress (OS) resulting from imbalance in the generation of reactive oxygen species (ROS) and/or the dysfunction of the antioxidant machinery, is a key mechanism associated with the onset of neurodegenerative disorders. Although the molecular mechanisms are still elusive, the onset of disorders such as Alzheimer's and Parkinson's disease have been associated with mitochondrial dysfunction. Recently, a mitochondrial-targeted hydrogen sulphide (H2S) donor, AP39, has shown to promote cellular bioenergetics in OS related scenarios. The aim of this study was to explore the potential of AP39 to protect the mitochondrial function in an OS environment induced by hydrogen peroxide (H2O2). We assessed the potential effects of increasing concentrations of AP39 on cell viability, H2S availability and the mitochondrial bioenergetic response in resting (non-differentiated and differentiated) neuroblastoma SHSY5Y cell line. Further, we explored the role of AP39 in attenuating H2O2-induced mitochondrial dysfunction. Our results showed that nanomolar to micromolar concentrations of AP39 (0.1 μM – 3 μM) are not toxic to SHSY5Y cells, regardless of their differentiation status. Fluorescence detection of H2S observed AP39 co-localises within the mitochondria in a concentration dependent manner. Whilst a lower concentration of AP39 (0.3 μM) was required to improve the mitochondrial bioenergetics in resting non-differentiated cells, 1 μM produced this effect in their differentiated counterparts. In both, non-differentiated and differentiated cells, AP39 reduced H2O2-induced mitochondrial impairments by improving the parameters of the mitochondrial function and abrogating the generation of mitochondrial ROS. These suggest that mitochondrial targeted delivery of H2S may attenuate neuronal toxicity in neuronal disorders associated with OS-induced mitochondrial dysfunction.Lissette Sanchez-ArangurenMandeep Kaur MarwahSarah NadeemElsevierarticleOxidative stressNeurodegenerative disordersMitochondrial dysfunctionHydrogen sulphide donorsBiochemistryQD415-436ENAdvances in Redox Research, Vol 3, Iss , Pp 100024- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Oxidative stress Neurodegenerative disorders Mitochondrial dysfunction Hydrogen sulphide donors Biochemistry QD415-436
spellingShingle	Oxidative stress Neurodegenerative disorders Mitochondrial dysfunction Hydrogen sulphide donors Biochemistry QD415-436 Lissette Sanchez-Aranguren Mandeep Kaur Marwah Sarah Nadeem Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
description	Oxidative stress (OS) resulting from imbalance in the generation of reactive oxygen species (ROS) and/or the dysfunction of the antioxidant machinery, is a key mechanism associated with the onset of neurodegenerative disorders. Although the molecular mechanisms are still elusive, the onset of disorders such as Alzheimer's and Parkinson's disease have been associated with mitochondrial dysfunction. Recently, a mitochondrial-targeted hydrogen sulphide (H2S) donor, AP39, has shown to promote cellular bioenergetics in OS related scenarios. The aim of this study was to explore the potential of AP39 to protect the mitochondrial function in an OS environment induced by hydrogen peroxide (H2O2). We assessed the potential effects of increasing concentrations of AP39 on cell viability, H2S availability and the mitochondrial bioenergetic response in resting (non-differentiated and differentiated) neuroblastoma SHSY5Y cell line. Further, we explored the role of AP39 in attenuating H2O2-induced mitochondrial dysfunction. Our results showed that nanomolar to micromolar concentrations of AP39 (0.1 μM – 3 μM) are not toxic to SHSY5Y cells, regardless of their differentiation status. Fluorescence detection of H2S observed AP39 co-localises within the mitochondria in a concentration dependent manner. Whilst a lower concentration of AP39 (0.3 μM) was required to improve the mitochondrial bioenergetics in resting non-differentiated cells, 1 μM produced this effect in their differentiated counterparts. In both, non-differentiated and differentiated cells, AP39 reduced H2O2-induced mitochondrial impairments by improving the parameters of the mitochondrial function and abrogating the generation of mitochondrial ROS. These suggest that mitochondrial targeted delivery of H2S may attenuate neuronal toxicity in neuronal disorders associated with OS-induced mitochondrial dysfunction.
format	article
author	Lissette Sanchez-Aranguren Mandeep Kaur Marwah Sarah Nadeem
author_facet	Lissette Sanchez-Aranguren Mandeep Kaur Marwah Sarah Nadeem
author_sort	Lissette Sanchez-Aranguren
title	Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
title_short	Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
title_full	Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
title_fullStr	Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
title_full_unstemmed	Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line
title_sort	neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, ap39 on h2o2-induced oxidative stress in human neuroblastoma shsy5y cell line
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f4f1928fd69a4c29b4da17353b058355
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Neuroprotective effects of mitochondrial-targeted hydrogen sulphide donor, AP39 on H2O2-induced oxidative stress in human neuroblastoma SHSY5Y cell line

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