Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7beta-hydroxycholesterol-, and 24(S)-hydroxycholesterol: Protective effects of alpha-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3).
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Date publication
février 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELAGE-MOURROUX Régis, Pr DELMAS Dominique, Dr LIZARD Gérard, Dr LIMAGNE Emeric
Tous les auteurs :
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
Lien Pubmed
Résumé
In demyelinating or non-demyelinating neurodegenerative diseases, increased levels of 7-ketocholesterol (7KC), 7beta-hydroxycholesterol (7beta-OHC) and 24(S)-hydroxycholesterol (24S-OHC) can be observed in brain lesions. In 158N murine oligodendrocytes, 7KC triggers a complex mode of cell death defined as oxiapoptophagy, involving simultaneous oxidative stress, apoptosis and autophagy. In these cells, 7KC as well as 7beta-OHC and 24S-OHC induce a decrease of cell proliferation evaluated by phase contrast microscopy, an alteration of mitochondrial activity quantified with the MTT test, an overproduction of reactive oxygen species revealed by staining with dihydroethidium and dihydrorhodamine 123, caspase-3 activation, PARP degradation, reduced expression of Bcl-2, and condensation and/or fragmentation of the nuclei which are typical criteria of oxidative stress and apoptosis. Moreover, 7KC, 7beta-OHC and 24S-OHC promote conversion of microtubule-associated protein light chain 3 (LC3-I) to LC3-II which is characteristic of autophagy. Consequently, 7beta-OHC and 24S-OHC, similarly to 7KC, can be considered as potent inducers of oxiapoptophagy. Furthermore, the different cytotoxic effects associated with 7KC, 7beta-OHC and 24S-OHC-induced oxiapoptophagy are attenuated by vitamin E (VitE, alpha-tocopherol) and DHA which enhances VitE protective effects. In 158N murine oligodendrocytes, our data support the concept that oxiapoptophagy, which can be inhibited by VitE and DHA, could be a particular mode of cell death elicited by cytotoxic oxysterols.
Référence
Steroids. 2015 Feb 12. pii: S0039-128X(15)00059-8