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Date publication

juin 2020

Journal

British journal of pharmacology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LIZARD Gérard


Tous les auteurs :
Nury T, Zarrouk A, Yammine A, Mackrill JJ, Vejux A, Lizard G

Résumé

Oxysterols are oxidized forms of cholesterol generated from cholesterol either by auto-oxidation, enzymatic processes or both. Some of them (7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells, nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of reactive oxygen species, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Apoptosis is associated with activation of the mitochondrial pathway: opening of the mitochondrial permeability pore, loss of mitochondrial membrane potential, caspase-3 activation, poly (ADP-ribose) polymerase (PARP) degradation, nuclear condensation and/or fragmentation. Autophagy is characterized by autophagic vacuoles revealed by monodansylcadaverine staining and transmission electron microscopy, and an increased ratio (LC-3II/LC-3I). In addition, morphological, topographical and functional changes of the peroxisome are observed.

Mots clés

7-ketocholesterol; 7β-hydroxycholesterol; 24(S)-hydroxycholesterol, cytoprotection, oxiapoptophagy, oxysterols

Référence

Br. J. Pharmacol.. 2020 Jun 24;: