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

Journal article


Ademowo, Opeyemi S., Dias, Irundika H.K., Diaz-Sanchez, Lorena, Sanchez-Aranguren, Lissette, Stahl, Wilhelm and Griffiths, Helen R. 2020. Partial mitigation of oxidized phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoids. Journal of Alzheimer's Disease. https://doi.org/10.3233/jad-190923
AuthorsAdemowo, Opeyemi S., Dias, Irundika H.K., Diaz-Sanchez, Lorena, Sanchez-Aranguren, Lissette, Stahl, Wilhelm and Griffiths, Helen R.
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.

KeywordsBioenergetics; POVPC; Carotenoids; Lutein; Mitochondria; Oxidative stress; Oxidized phospholipids; Viability; Zeaxanthin.
Year2020
JournalJournal of Alzheimer's Disease
PublisherIOS Press
ISSN1387-2877
1875-8908
Digital Object Identifier (DOI)https://doi.org/10.3233/jad-190923
Web address (URL)http://hdl.handle.net/10545/624543
http://creativecommons.org/licenses/by-nc-nd/4.0/
hdl:10545/624543
Publication dates20 Jan 2020
Publication process dates
Deposited05 Mar 2020, 09:40
Accepted20 Dec 2019
Rights

Attribution-NonCommercial-NoDerivatives 4.0 International

ContributorsAston University, Birmingham, West Midlands, UK, Institute of Biochemistry and Molecular Biology, Germany and University of Surrey
File
File Access Level
Open
File
File Access Level
Open
File
Permalink -

https://repository.derby.ac.uk/item/93yz6/partial-mitigation-of-oxidized-phospholipid-mediated-mitochondrial-dysfunction-in-neuronal-cells-by-oxocarotenoids

Download files

  • 20
    total views
  • 4
    total downloads
  • 0
    views this month
  • 1
    downloads this month

Export as

Related outputs

Effects of carotenoids on mitochondrial dysfunction
Ademowo, S., Oyebode, O., Edward, R., Conway, M., Griffiths, H. and Dias, I. H. K. 2024. Effects of carotenoids on mitochondrial dysfunction. Biochemical Society Transactions. 52 (1), p. 65–74. https://doi.org/10.1042/BST20230193
Circulating oxysterols in Alzheimer’s disease: a systematic review and meta-analysis
Ademowo, OS. and Dias, I. H. K 2022. Circulating oxysterols in Alzheimer’s disease: a systematic review and meta-analysis. Redox Experimental Medicine. 2022 (1), pp. 116 -126. https://doi.org/10.1530/REM-22-0009
Inflammation, lipid (per)oxidation, and redox regulation
Dias, Irundika H.K., Milic, Ivana, Heiss, Christian, Ademowo, Opeyemi S., Polidori, Maria Cristina, Devitt, Andrew and Griffiths, Helen R. 2020. Inflammation, lipid (per)oxidation, and redox regulation. Antioxidant and Redox Signaling. https://doi.org/10.1089/ars.2020.8022
Nutritional hormesis in a modern environment
Ademowo, O. Stella, Dias, H. K. Irundika, Pararasa, Chathyan and Griffiths, Helen R. 2018. Nutritional hormesis in a modern environment. in: The Science of Hormesis in Health and Longevity Elsevier.
Discovery and confirmation of a protein biomarker panel with potential to predict response to biological therapy in psoriatic arthritis
Ademowo, Opeyemi S, Hernandez, Belinda, Collins, Emily, Rooney, Cathy, Fearon, Ursula, van Kuijk, Arno W, Tak, Paul-P, Gerlag, Danielle M, FitzGerald, Oliver and Pennington, Stephen R 2014. Discovery and confirmation of a protein biomarker panel with potential to predict response to biological therapy in psoriatic arthritis. Annals of the Rheumatic Diseases. 75 (1), pp. 234-241. https://doi.org/10.1136/annrheumdis-2014-205417
Distribution of plasma oxidised phosphatidylcholines in chronic kidney disease and periodontitis as a co-morbidity
Ademowo, Opeyemi Stella, Sharma, Praveen, Cockwell, Paul, Reis, Ana, Chapple, Iain L., Griffiths, Helen R. and Dias, Irundika H.K. 2019. Distribution of plasma oxidised phosphatidylcholines in chronic kidney disease and periodontitis as a co-morbidity. Free Radical Biology and Medicine. 146, pp. 130-138. https://doi.org/10.1016/j.freeradbiomed.2019.10.012
Lipid (per) oxidation in mitochondria: an emerging target in the ageing process?
Ademowo, O. S., Dias, H. K. I., Burton, D. G. A. and Griffiths, H. R. 2017. Lipid (per) oxidation in mitochondria: an emerging target in the ageing process? Biogerontology. 18 (6), pp. 859-879. https://doi.org/10.1007/s10522-017-9710-z
European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)
Egea, Javier, Fabregat, Isabel, Frapart, Yves M., Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G., Lopez, Manuela G., Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul, Abbas, Kahina, Ademowo, Opeyemi S., Afonso, Catarina B., Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M., Barbosa, Rui M., Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P., Brito, Paula M., Carrara, Guia, Casas, Ana I., Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S., Costa, João G., Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec–Butuner, Bilge, Dias, Irundika H.K., Dunn, Joe Dan, Edson, Amanda J., El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S., Fladmark, Kari E., Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A., Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J., Meredith, Stuart P., Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T.N., Oelze, Matthias, Oliveira, Nuno G., Palmeira, Carlos M., Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G., Pitt, Andrew R., Poulsen, Henrik E., Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P., Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L., Soldati, Thierry, Sousa, Bebiana C., Spickett, Corinne M., Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A., Yalçın, A. Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M., Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H.H.W., Di Lisa, Fabio and Daiber, Andreas 2017. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biology. 13, pp. 94-162. https://doi.org/10.1016/j.redox.2017.05.007
Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients
Ademowo, O.S., Dias, H.K.I., Milic, I., Devitt, A., Moran, R., Mulcahy, R., Howard, A.N., Nolan, J.M. and Griffiths, H.R. 2017. Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients. Free Radical Biology and Medicine. 108, pp. 77-85. https://doi.org/10.1016/j.freeradbiomed.2017.03.008