title: In vitro study of the direct effect of extracellular hemoglobin on myelin components.
abstract: There is a relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of dilated veins in MS plaques. The sources of this iron can be varied, but capillary and venous hemorrhages leading to blood extravasation have been recorded, and could result in the release of hemoglobin extracellularly. Extracellular hemoglobin oxidizes quickly and is known to become a reactive molecule that triggers low-density lipoprotein oxidation and plays a pivotal role in atherogenesis. In MS, it could lead to local oxidative stress, inflammation, and tissue damage. Here, we investigated whether extracellular hemoglobin and its breakdown products can cause direct oxidative damage to myelin components in a peroxidative environment such as occurs in inflamed tissue. Oxidation of lipids was assessed by the formation of fluorescent peroxidized lipid-protein covalent adducts, by the increase in conjugated diene and malondialdehyde. Oxidation of proteins was analyzed by the change in protein mass. The results suggest that the globin radical could be a trigger of myelin basic protein oxidative cross-linking, and that heme transferred to the lipids is involved in lipid peroxidation. This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Bamm
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Lanthier
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Stephenson
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Graham S T
authors.initials: GS
authors.lastname: Smith
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada. Electronic address: gharauz@uoguelph.ca.
authors.forename: George
authors.initials: G
authors.lastname: Harauz
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D005110:Extracellular Space / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D006454:Hemoglobins
keywords: Globin radical; Hemoglobin; Multiple sclerosis; Myelin; Myelin basic protein; Oxidative stress