α-Tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving GSK-3 activation and Mcl-1 degradation on 158N murine oligodendrocytes

6533b820fe1ef96bd127a410

RESEARCH PRODUCT

α-Tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving GSK-3 activation and Mcl-1 degradation on 158N murine oligodendrocytes

Gérard Lizard Kévin Ragot Thomas Nury Dominique Delmas Mauhamad Baarine Anne Athias

subject

Programmed cell death Time Factors Cell Survival alpha-Tocopherol Apoptosis Caspase 3 Biochemistry Dephosphorylation Glycogen Synthase Kinase 3 Mice Membrane Microdomains GSK-3 Animals Ketocholesterols Molecular Biology Protein kinase B Cell Proliferation Membrane Potential Mitochondrial Phospholipidosis Glycogen Synthase Kinase 3 beta Caspase 3 Chemistry Organic Chemistry Cytochromes c Cell Biology Cell biology Enzyme Activation Oligodendroglia Protein Transport Proto-Oncogene Proteins c-bcl-2 Apoptosis Myeloid Cell Leukemia Sequence 1 Protein DNA fragmentation

description

Abstract In important and severe neurodegenerative pathologies, 7-ketocholesterol, mainly resulting from cholesterol autoxidation, may contribute to dys- or demyelination processes. On various cell types, 7-ketocholesterol has often been shown to induce a complex mode of cell death by apoptosis associated with phospholipidosis. On 158N murine oligodendrocytes treated with 7-ketocholesterol (20 μg/mL corresponding to 50 μM, 24–48 h), the induction of a mode of cell death by apoptosis characterised by the occurrence of cells with condensed and/or fragmented nuclei, caspase activation (including caspase-3) and internucleosomal DNA fragmentation was observed. It was associated with a loss of transmembrane mitochondrial potential (ΔΨm) measured with JC-1, with a dephosphorylation of Akt and GSK3 (especially GSK3β), and with degradation of Mcl-1. With α-tocopherol (400 μM), which was capable of counteracting 7-ketocholesterol-induced apoptosis, Akt and GSK3β dephosphorylation were inhibited as well as Mcl-1 degradation. These data underline that the potential protective effects of α-tocopherol against 7-ketocholesterol-induced apoptosis do not depend on the cell line considered, and that the cascade of events (Akt/GSK3β/Mcl-1) constitutes a link between 7-ketocholesterol-induced cytoplasmic membrane dysfunctions and mitochondrial depolarisation leading to apoptosis.

year	journal	country	edition	language
2011-09-01	Chemistry and Physics of Lipids

https://doi.org/10.1016/j.chemphyslip.2011.04.014