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Partial mitigation of oxidised phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoids

Ademowo, Opeyemi S, Dias, Irundika HK, Diaz-Sanchez, Lorena, Sanchez-Aranguren, Lissette, Stahl, Wilhelm and Griffiths, Helen (2020) Partial mitigation of oxidised phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoids Journal of Alzheimer's Disease.

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Mitochondria are important (patho)physiological sources of reactive oxygen species (ROS) that mediate mitochondrial dysfunction and phospholipid oxidation; an increase in mitochondrial content of oxidised phospholipid (OxPL) associates with cell death. Previously we showed that the circulating OxPL 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) increases in patients with Alzheimer’s disease (AD), and associates with lower plasma antioxidant oxocarotenoids, zeaxanthin and lutein. Since oxocarotenoids are metabolised in mitochondria, we propose that during AD, lower concentrations of mitochondrial zeaxanthin and lutein may result in greater phospholipid oxidation and predispose to neurodegeneration. Here, we have investigated whether non-toxic POVPC concentrations impair mitochondrial metabolism in differentiated (d)SH-SY5Y neuronal cells and whether there is any protective role for oxocarotenoids against mitochondrial dysfunction. After 24 hours, glutathione (GSH) concentration was lower in neuronal cells exposed to POVPC (1-20μM) compared with vehicle control without loss of viability compared to control. However, mitochondrial ROS production (determined by MitoSOX oxidation) was increased by 50% only after 20μM POVPC. Following delivery of lutein (0.1-1μM) and zeaxanthin (0.5-5μM) over 24 hours in vitro, oxocarotenoid recovery from dSH-SY5Y cells was >50%. Co-incubation with oxocarotenoids prevented loss of GSH after 1μM but not 20μM POVPC, whereas the increase in ROS production induced by 20μM POVPC was prevented by lutein and zeaxanthin. Mitochondrial uncoupling increases and ATP production is inhibited by 20μM but not 1 μM POVPC; carotenoids protected against uncoupling although did not restore ATP production. In summary, 20μM POVPC induced loss of GSH and a mitochondrial bioenergetic deficit in neuronal cells that was not mitigated by oxocarotenoids.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Ademowo, Opeyemi S
Dias, Irundika HK
Diaz-Sanchez, Lorena
Sanchez-Aranguren, Lissette
Stahl, Wilhelm
Date : 20 January 2020
Funders : Aston Research Centre for Healthy Ageing
OA Location :
Grant Title : Kidney Research Foundation
Uncontrolled Keywords : Carotenoids, oxidative stress, mitochondria, viability, oxidised phospholipids, lutein, zeaxanthin, bioenergetics, POVPC
Depositing User : James Marshall
Date Deposited : 18 Feb 2020 15:24
Last Modified : 18 Feb 2020 15:24

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