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 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.

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Divisions: College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > Aston Medical School
Additional Information: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Funding: This work was funded by the Sir Halley Stewart Trust (Ref number 2728).
Publication ISSN: 2667-1379
Last Modified: 15 Apr 2024 07:39
Date Deposited: 22 Nov 2021 08:28
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Related URLs: https://www.sci ... 0242?via%3Dihub (Publisher URL)
PURE Output Type: Article
Published Date: 2021-11-18
Published Online Date: 2021-11-18
Accepted Date: 2021-11-10
Authors: Sanchez-Aranguren, Lissette (ORCID Profile 0000-0002-4663-5752)
Marwah, Mandeep Kaur (ORCID Profile 0000-0003-4881-003X)
Nadeem, Sarah

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