Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes

摘要: There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC), are increased in the plasma patients with neurodegenerative diseases associated demyelinization central nervous system (CNS). It was therefore interest to investigate effects these oxysterols on oligodendrocytes, myelin-forming cells CNS. To this end, 158N murine oligodendrocytes were treated 7KC or 7βOHC inducing an apoptotic mode cell death characterized by condensation/fragmentation nuclei, dephosphorylation Akt GSK3, mitochondrial depolarization involving Mcl-1, caspase-3 activation. In contrast, under treatment 27-hydroxycholesterol (27OHC), no observed. When stained Fura-2, significant Ca2+ rise found different oxysterols, whereas strong signals detected ionomycin used as positive control. At concentrations which induced apoptosis, but not accumulated lipid rafts. Although cytotoxic, 27OHC mainly noteworthy α-tocopherol (but ellagic acid resveratrol) able counteract 7KC- 7βOHC-induced apoptosis decrease accumulation Thus, cells, ability trigger a GSK-3 activation independent increase level their raft microdomains.