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Hypochlorite‐induced white matter damage
Author(s) -
Konat G. W.,
Tirumalai P.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.16_7.x
Subject(s) - myelin , labelling , white matter , chemistry , biochemistry , leucine , ganglioside , toxicity , proteolipid protein 1 , myelin basic protein , biology , endocrinology , central nervous system , medicine , amino acid , organic chemistry , magnetic resonance imaging , radiology
The extent and severity of inflammation‐mediated white matter destruction correlates with neutrophil infiltration. Although the mechanisms are not fully understood, the generation of vast quantities of hypochlorite (HC) by activated neutrophils may be the major damaging factor. This study was undertaken to determine the toxicity of HC to white matter using brain stem slices from 2 month‐old female rats. Because of its high volatility under the incubation conditions (half‐life of ∼ 7.5 min), HC was administered every 30 min as 1 m m boluses providing an average concentration of ∼ 0.27 m m . Exposure period (1–3 h) was followed by 1 h recovery in normal medium, and by 2 h labelling with 3 H‐leucine. Subsequently, slices were homogenized, and myelin was isolated by sucrose gradient ultracentrifugation. HC exposure inhibited total homogenate protein synthesis in the concentration‐ and time‐dependent manner. Thus, following 1, 2 and 3 h of exposure, total homogenate protein synthesis was reduced to ∼ 65, 45 and 30% of control. HC exposure preferentially suppressed the assembly of major structural proteins into the myelin sheath. Thus, 1 h exposure reduced the assembly of proteolipid protein and basic protein to ∼ 30% of control value. A significant amount of 3 H‐leucine was also incorporated into myelin lipids. Unexpectedly, HC exposure profoundly stimulated 3 H‐labelling of myelin lipids. Thus, after 1 and 2 h of exposure the labelling of myelin lipids was increased by ∼ 40 and 90% over control, respectively. In contrast, the labelling of nonmyelin lipids decreased to ∼ 50% of control. These results demonstrate that HC drastically alters myelin metabolism, and thus, may underlie neutrophil‐mediated inflammatory demyelination in multiple sclerosis. Acknowledgements: Supported by NMSS research grant 3067A1.