Potential role of ferric hemoglobin in MS pathogenesis: Effects of oxidative stress and extracellular methemoglobin or its degradation products on myelin components.

Potential role of ferric hemoglobin in MS pathogenesis: Effects of oxidative stress and extracellular methemoglobin or its degradation products on myelin components. Free Radic Biol Med. 2017 Aug 29;: Authors: Bamm VV, Henein MEL, Sproul SLJ, Lanthier DK, Harauz G Abstract There is a well-documented relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of the dilated veins in cerebral MS plaques. The source of this iron is unknown, but could be related to the recognized phenomenon of capillary and venous hemorrhages leading to blood extravasation. In turn, hemorrhaging leading to hemolysis results in extracellular release of hemoglobin, a reactive molecule that could induce local oxidative stress, inflammation, and tissue damage. Our previous studies with a reduced form of hemoglobin (oxyHb) have demonstrated its ability to cause extensive lipid and protein oxidation in vitro, which would result in membrane destabilization. Here, we investigated in further detail the mechanism by which the more abundant oxidized form of extracellular hemoglobin (metHb), and dissociated hemin, cause direct oxidative damage to myelin components, specifically membrane-mimetic lipid vesicles and myelin basic protein (MBP), a highly-abundant protein in the CNS. Oxidation of lipids was assessed by the formation of conjugated diene/triene and malondialdehyde, and oxidation ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research