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In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy

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Implication of Oxysterols and Phytosterols in Aging and Human Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1440))

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Abstract

7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer’s disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome. These changes can be revealed by fluorescence microscopy (apotome, confocal microscopy), transmission electron microscopy, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and gas chromatography-coupled with mass spectrometry (GC-MS). Noteworthy, several natural molecules, including ω3 fatty acids, polyphenols, and α-tocopherol, as well as several Mediterranean oils [argan and olive oils, Milk-thistle (Sylibum marianum) and Pistacia lenticus seed oils], have cytoprotective properties and attenuate 7-ketocholesterol- and 7β-hydroxycholesterol-induced peroxisomal modifications. These observations led to the concept of pexotherapy.

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Abbreviations

7KC:

7-Ketocholesterol

7β-OHC:

7β-Hydroxycholesterol

Abcd transporter:

ATP-binding cassette sub-type D transporter

Acox1:

Acyl-CoA oxidase 1

AMD:

Age-related macular degeneration

AO:

Argan oil

DHA:

Docosahexaenoic acid

DHAP-AT:

Dihydroxyacetone-phosphate acyltransferase

ELOVL:

Fatty acid elongase

GC-MS:

Gas chromatography-coupled with mass spectrometry

GPx:

Glutathione peroxidase

Mfp2:

Peroxisomal multifunctional protein-2

PLSO:

Pistacia lenticus seed oil

RT-qPCR:

Quantitative reverse transcription polymerase chain reaction

SOD:

Superoxide dismutase

TEM:

Transmission electron microscopy

VLCFA:

Very-long chain fatty acid

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Acknowledgments

The authors would like to thank Prof. Hervé Alexandre (Institut Universitaire de la Vigne et du Vin, Université de Bourgogne, Dijon, France) for providing the flow cytometer. Imen Ghzaiel, Mohamed Ksila, and Aline Yammine received financial support from ABASIM (Association Bourguignonne pour les Applications des Sciences de l’Information en Médecine (Dijon, France) and/or Nutrition Méditérranéenne et Santé (NMS; President Prof. Norbert Latruffe). This work was also funded by the Université de Bourgogne (Dijon, France), the University of Monastir (Monastir, Tunisia), and the University of Tunis El Manar (Tunis, Tunisia). This work (PhD Thesis; Mohamed Ksila) was also in part supported by PHC Utique (2022 and 2023, Code CMCU: 22G0809/Code Campus France: 47608VJ); Dr. Gérard Lizard/Prof. Taoufik Ghrairi; University Tunis El Manar (Tunis, Tunisie); University of Monastir (Monastir, Tunisia); University of Gabès (Gabès, Tunisia); Faculty of Science and Technology, University Hassan I (Settat, Morocco).

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Bio-PeroxIL Laboratory, EA7270, University of Bourgogne & Inserm, Dijon, France

    Imen Ghzaiel, Mohamed Ksila, Amira Namsi, Aline Yammine, Meriam Debbabi, Asma Badreddine, Wiem Meddeb, Vivien Pires, Thomas Nury, Mauhamad Baarine, Anne Vejux & Gérard Lizard

  2. Faculty of Medicine, Laboratory ‘Nutrition, Functional Food and Vascular Health’ (LR12ES05), University of Monastir, Monastir, Tunisia

    Imen Ghzaiel, Amira Zarrouk, Sonia Hammami & Mohamed Hammami

  3. Laboratory of Rangeland Ecosystems and Valorization of Spontaneous Plants and Associated Microorganisms (LR16IRA03), Arid Regions Institute, University of Gabes, Medenine, Tunisia

    Samah Maaloul & Raoudha Abdellaoui

  4. Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules (LR18ES03), Department of Biology, Faculty of Sciences, University Tunis El Manar, Tunis, Tunisia

    Mohamed Ksila, Olfa Masmoudi-Kouki & Taoufik Ghrairi

  5. Laboratory of Biochemistry, Neuroscience, Natural Resources and Environment, Faculty of Science and Technology, University Hassan I, Settat, Morocco

    Asma Badreddine & Boubker Nasser

  6. Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, Dijon, France

    Franck Ménétrier

  7. Agroécologie, AgroSup Dijon, CNRS, INRAE, University Bourgogne Franche-Comté, Plateforme DimaCell, Dijon, France

    Laure Avoscan

  8. Faculty of Medicine, University of Sousse, Laboratory of Biochemistry, Sousse, Tunisia

    Amira Zarrouk

  9. LCPMC-A2, ICPM, Department of Chemistry, University Lorraine, Metz Technopôle, Metz, France

    Mohammad Samadi

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  1. Imen Ghzaiel
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Corresponding author

Correspondence to Gérard Lizard .

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Editors and Affiliations

  1. Department of Biochemistry (Biochemstry of the peroxisome, inflammation and lipid metabolism), University of Bourgogne & Inserm, Dijon, France

    Gérard Lizard

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Ghzaiel, I. et al. (2024). In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy. In: Lizard, G. (eds) Implication of Oxysterols and Phytosterols in Aging and Human Diseases. Advances in Experimental Medicine and Biology, vol 1440. Springer, Cham. https://doi.org/10.1007/978-3-031-43883-7_21

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