Team: Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism; Lab. Bio-peroxIL / EA7270; Université de Bourgogne-Franche Comté; Dijon - France
Key members: Gérard Lizard (PI, PhD, Inserm/UBFC), Anne Vejux (PhD, UBFC), Thomas Nury (PhD, UBFC), Thibault Moreau (MD-PhD, Univ. Hospital-UBFC)
PhD students: Khouloud SASSI; Aline YAMMINE; Imen GHZAIEL
Contacts: ; ;
Research activities: In the context of atherosclerosis (1994-2005); the team has been the first to describe pro-oxidative and pro-apoptotic properties of oxysterols, especially of oxysterols resulting from cholesterol auto-oxidation such as 7-ketocholesterol (7KC). We described the signaling pathways associated with the pro-apoptotic and pro-oxidant activities of 7KC. This leads us to identify synthetic and natural compounds, and mixtures of molecules, capable to prevent 7KC-induced side effects. We were also among the first to report the pro-inflammatory properties of oxysterols, including 25-hydroxycholesterol. In 2003, we introduced the name oxiapoptophagy which summarizes that oxysterol-induced cell death, triggered by some oxysterols, simultaneously induces OXIdative stress, APOPTOsis and autoPHAGY. In this cell death process, major mitochondrial and lysosomal dysfunctions associated with a reticulum stress have been observed. Since 2006, we are interested by the part taken by oxysterols in neurodegenerative diseases: adrenoleucodystrophy (x-ALD), Alzheimer’s disease, multiple sclerosis (MS). We reported that some oxysterols induce oxiapoptophagy in neuronal cells. We try to precise the part taken by the peroxisome in nerve cell dysfunctions (especially oxidation and inflammation leading to cell death) and demyelination. In this context, basic and clinical researchs are conducted. We attempt to identify molecules capable to impair all or part of the oxiapoptophagic process (Ongoing PhD Theses: Aline YAMMINE; Imen GHZAIEL). In X-ALD and MS, we attempt to identify lipid biomarkers (oxysterols, fatty acids, phospholipids), and to develop new treatments (targeted therapies, nanotherapies (theranostic)). Currently, we are also interested in the metabolic therapy of glioblastoma using cholesterol derivatives (Ongoing PhD Thesis, Khouloud SASSI).
Key papers related to ENOR:
Nury T, Zarrouk A, Ragot K, Debbabi M, Riedinger JM, Vejux A, Aubourg P, Lizard G. 7-Ketocholesterol is increased in the plasma of X-ALD patients and induces peroxisomal modifications in microglial cells: Potential roles of 7-ketocholesterol in the pathophysiology of X-ALD. J Steroid Biochem Mol Biol. 2017; 169: 123-136.
Nury T, Zarrouk A, Mackrill JJ, Samadi M, Durand P, Riedinger JM, Doria M, Vejux A, Limagne E, Delmas D, Prost M, Moreau T, Hammami M, Delage-Mourroux R, O'Brien NM, Lizard G. Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7β-hydroxycholesterol-, or 24(S)-hydroxycholesterol: Protective effects of α-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3). Steroids. 2015; 99(Pt B): 194-203.
Nury T, Zarrouk A, Vejux A, Doria M, Riedinger JM, Delage-Mourroux R, Lizard G. Induction of oxiapoptophagy, a mixed mode of cell death associated with oxidative stress, apoptosis and autophagy, on 7-ketocholesterol-treated 158N murine oligodendrocytes: impairment by α-tocopherol. Biochem Biophys Res Commun. 2014; 446(3): 714-9.
Lemaire-Ewing S, Prunet C, Montange T, Vejux A, Berthier A, Bessède G, Corcos L, Gambert P, Néel D, Lizard G. Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols. Cell Biol Toxicol. 2005; 21(2): 97-114.
Miguet C, Monier S, Bettaieb A, Athias A, Besséde G, Laubriet A, Lemaire S, Néel D, Gambert P, Lizard G. Ceramide generation occurring during 7beta-hydroxycholesterol- and 7-ketocholesterol-induced apoptosis is caspase independent and is not required to trigger cell death. Cell Death Differ. 2001; 8(1): 83-99.
Lizard G, Gueldry S, Sordet O, Monier S, Athias A, Miguet C, Bessede G, Lemaire S, Solary E, Gambert P. Glutathione is implied in the control of 7-ketocholesterol-induced apoptosis, which is associated with radical oxygen species production. FASEB J. 1998; 12(15): 1651-63.
Lizard G, Deckert V, Dubrez L, Moisant M, Gambert P, Lagrost L. Induction of apoptosis in endothelial cells treated with cholesterol oxides. Am J Pathol. 1996, 148(5): 1625-38.
Vejux A, Namsi A, Nury T, Moreau T, Lizard G. Biomarkers of amyotrophic lateral sclerosis: current status and interest of oxysterols and phytosterols. Front Mol Neurosci; doi: 10.3389/fnmol2018.00012
Doria M, Maugest L, Moreau T, Lizard G, Vejux A. Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson's disease. Free Radic Biol Med.; 101: 393-400.
Trompier D, Vejux A, Zarrouk A, Gondcaille C, Geillon F, Nury T, Savary S, Lizard G. Brain peroxisomes. Biochimie. 2014; 98: 102-110.
Vejux A, Lizard G. Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med. 2009; 30(3): 153-170.