title: Plasmalogen phospholipids protect internodal myelin from oxidative damage.
abstract: Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin.
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Adrienne M
authors: AM
authors: Luoma
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Fonghsu
authors: F
authors: Kuo
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Ozgur
authors: O
authors: Cakici
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Michelle N
authors: MN
authors: Crowther
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Andrew R
authors: AR
authors: Denninger
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA.
authors: Robin L
authors: RL
authors: Avila
authors: Nerve Regeneration Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors: Pedro
authors: P
authors: Brites
authors: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467-3811, USA. Electronic address: kirschnd@bc.edu.
authors: Daniel A
authors: DA
authors: Kirschner
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000494:pharmacology; D005561:Formates / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000074437:Peroxisomal Targeting Signal 2 Receptor; D010955:Plasmalogens / Q000494:pharmacology*; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology
chemical_list: D002614:Chelating Agents; D005561:Formates; D016166:Free Radical Scavengers; D000074437:Peroxisomal Targeting Signal 2 Receptor; D010955:Plasmalogens; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; C030544:formic acid; D004492:Edetic Acid
keywords: Ascorbate; Membranes; Myelin; Optic nerve; Oxidative damage; Plasmalogen lipids; Sciatic nerve; X-ray diffraction