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Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis
Author(s) -
Jack Carolyn,
Antel Jack,
Brück Wolfgang,
Kuhlmann Tanja
Publication year - 2007
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20514
Subject(s) - peroxynitrite , oligodendrocyte , multiple sclerosis , nitric oxide , nitrotyrosine , biology , neuroglia , microglia , nitric oxide synthase , microbiology and biotechnology , programmed cell death , immunology , myelin , inflammation , biochemistry , neuroscience , apoptosis , central nervous system , superoxide , endocrinology , enzyme
Abstract Nitric oxide (NO) and peroxynitrite (ONOO − ) are potential mediators of the injury and cytotoxicity occurring over time to oligodendrocytes in multiple sclerosis (MS) lesions. Our in vitro results indicate that human adult CNS‐derived oligodendrocytes are relatively resistant to NO‐mediated damage. In contrast, human oligodendrocytes are highly susceptible to peroxynitrite‐mediated injury. In situ , we found that inducible nitric oxide synthase (iNOS) was expressed in astrocytes and macrophages in all active demyelinating and remyelinating MS lesions examined, yet no correlation was found between numbers of glial cells expressing iNOS and the extent of oligodendrocyte cell death. Nitrotyrosine groups, indicative of the presence of peroxynitrite in vivo , could be detected on astrocytes, macrophages, and oligodendrocytes in MS lesions. High numbers of nitrotyrosine‐positive oligodendrocytes were found in one MS case that featured extensive oligodendrocyte cell death. Our results indicate that NO alone is unlikely to induce oligodendrocyte injury, whereas its more potent byproduct peroxynitrite is a potential mediator of injury to oligodendrocytes in MS. © 2007 Wiley‐Liss, Inc.