Partial Mitigation of Oxidized Phospholipid-Mediated Mitochondrial Dysfunction in Neuronal Cells by Oxocarotenoids

Abstract

Mitochondria are important (patho)physiological sources of reactive oxygen species (ROS) that mediate mitochondrial dysfunction and phospholipid oxidation; an increase in mitochondrial content of oxidized 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 metabolized 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 1μM 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.

Publication DOI: https://doi.org/10.3233/JAD-190923
Divisions: Aston Medical School
Life & Health Sciences > Biosciences
Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: Copyright ©2020 IOS Press All rights reserved. Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2019
Uncontrolled Keywords: Bioenergetics,POVPC,carotenoids,lutein,mitochondria,oxidative stress,oxidized phospholipids,viability,zeaxanthin,Neuroscience(all),Clinical Psychology,Geriatrics and Gerontology,Psychiatry and Mental health
Full Text Link:
Related URLs: https://content ... sease/jad190923 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-03-10
Published Online Date: 2020-01-20
Accepted Date: 2019-12-20
Authors: Ademowo, Opeyemi Stella
Dias, Irundika ( 0000-0002-6620-8221)
Diaz Sanchez, Lorena
Sanchez Aranguren, Lissette ( 0000-0002-4663-5752)
Stahl, Wilhelm
Griffiths, Helen

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