Induction of peroxisomal changes in oligodendrocytes treated with 7-ketocholesterol: Attenuation by α-tocopherol

Under treatment with 7-ketocholesterol (7 KC), a concentration dependent overproduction of superoxide anion (O2●-) and hydrogen peroxide (H2O2) was observed with 7 KC (25, 50 μM). At the lowest concentration of 7 KC (25 μM), minor mitochondrial dysfunctions were revealed: ΔΨm was slightly affected and a slight decrease of cardiolipins was detected. However, important mitochondrial topographical changes were observed. At the highest concentration of 7 KC (50 μM), an important loss of ΔΨm associated with a marked decrease of cardiolipins was observed, and the mitochondrial topographical changes were more pronounced. However, peroxisomal dysfunctions (topographical, morphological and functional) were found on 158 N murine oligodendrocytes both at a low concentration of 7 KC (25 μM), which does not trigger oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY), and at a cytotoxic concentration of 7 KC (50 μM) which induces an oxiapoptophagic mode of cell death. Thus, with 7 KC (25 μM) no sign of apoptosis was detected (no cleaved-caspase-3, and no cleaved PARP), whereas a slight increase of the ratio (LC3-II/LC3-I), which is an autophagic criteria, was revealed (probable occurrence of pexophagy). At a highest concentration (7 KC: 50 μM), peroxisomal and mitochondrial dysfunctions were exacerbated, as well as overproduction of superoxide anion (O2●-) and hydrogen peroxide (H2O2). In agreement with previous data obtained on different cell lines, 7 KC-induced side effects (mitochondrial as well as peroxisomal dysfunctions, cell death induction) were strongly attenuated by α-tocopherol whereas no cytoprotective effects were observed with α-tocotrienol.223