title: Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability.
abstract: Oxidative phosphorylation (OXPHOS) is not only the main source of ATP for the cell, but also a major source of reactive oxygen species (ROS), which lead to oxidative stress. At present, mitochondria are considered the organelles responsible for the OXPHOS, but in the last years we have demonstrated that it can also occur outside the mitochondrion. Myelin sheath is able to conduct an aerobic metabolism, producing ATP that we have hypothesized is transferred to the axon, to support its energetic demand. In this work, spectrophotometric, cytofluorimetric, and luminometric analyses were employed to investigate the oxidative stress production in isolated myelin, as far as its respiratory activity is concerned. We have evaluated the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), markers of lipid peroxidation, as well as of hydrogen peroxide (H2O2), marker of ROS production. To assess the presence of endogenous antioxidant systems, superoxide dismutase, catalase, and glutathione peroxidase activities were assayed. The effect of certain uncoupling or antioxidant molecules on oxidative stress in myelin was also investigated. We report that isolated myelin produces high levels of MDA, 4-HNE, and H2O2, likely through the pathway composed by Complex I-III-IV, but it also contains active superoxide dismutase, catalase, and glutathione peroxidase, as antioxidant defense. Uncoupling compounds or Complex I inhibitors increase oxidative stress, while antioxidant compounds limit ROS generation. Data may shed new light on the role of myelin sheath in physiology and pathology. In particular, it can be presumed that the axonal degeneration associated with myelin loss in demyelinating diseases is related to oxidative stress caused by impaired OXPHOS.
authors.affiliation: Department of Pharmacy (DIFAR), Biochemistry Laboratory, University of Genova , Genova , Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ravera
authors.forename: M
authors.initials: M
authors.lastname: Bartolucci
authors.forename: P
authors.initials: P
authors.lastname: Cuccarolo
authors.forename: E
authors.initials: E
authors.lastname: Litamè
authors.forename: M
authors.initials: M
authors.lastname: Illarcio
authors.forename: D
authors.initials: D
authors.lastname: Calzia
authors.forename: P
authors.initials: P
authors.lastname: Degan
authors.forename: A
authors.initials: A
authors.lastname: Morelli
authors.forename: I
authors.initials: I
authors.lastname: Panfoli
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D005434:Flow Cytometry; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000737:chemistry; D008928:Mitochondria / Q000473:pathology; D009186:Myelin Sheath / Q000737:chemistry*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D016548:Prosencephalon; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: OXPHOS; ROS production; antioxidants; malondialdehyde; myelin energetic metabolism