Neurochem Res. 2004 Sep;29(9):1675-85. Related Articles, Links

Exposure of rat optic nerves to nitric oxide causes protein
S-nitrosation and myelin decompaction.

Bizzozero OA, DeJesus G, Howard TA.

Department of Cell Biology & Physiology, University of New
Mexico-Health Sciences Center, Albuquerque, New Mexico 87131, USA.
obizzozero@salud.unm.edu

This study investigates the effect of nitric oxide (NO) on both the
chemical modifications of CNS proteins and the architecture of the
myelinated internode. Incubation of rat optic nerves for 2 h with 1 mM
concentration of the NO-donors S-nitroso-N-acetyl-penicillamine (SNAP),
ethyl-2-[hydroxyimino]-5-nitro-3-hexeneamide (NOR-3), and
4-phenyl-3-furoxan carbonitrile (PFC) led to decompaction of myelin at
the level of the intraperiod line (IPL). In contrast, incubation with 1
mM sodium nitroprusside, which slowly releases NO, sodium nitrite, and
N-nitrosopyrrolidine failed to cause myelin disassembly. This suggests
that free NO and/or some of its direct oxidation products (e.g., N2O3)
are the active molecular species. NO-induced alterations in myelin
architecture could not be assigned to protein or lipid degradation,
lipid peroxidation, ATP depletion, calcium uptake, protein nitration,
protein carbonylation, and nerve depolarization. NO-treatment, however,
resulted in the S-nitrosation of a number of proteins. In myelin, one
of the major S-nitrosated substrates was identified as proteolipid
protein (PLP), an abundant cysteine-rich protein that is responsible
for IPL stabilization. Peripheral nervous system myelin, whose
stability depends on proteins other than PLP, was not decompacted upon
incubation of sciatic nerves with SNAP. It is proposed that NO-mediated
nitrosation of sulfhydryl groups is likely to interfere with the normal
function of PLP and other important CNS myelin proteins leading to the
structural demise of this membrane. These findings are relevant to
multiple sclerosis and other inflammatory demyelinating disorders where
both excessive NO production and myelin instability are known to occur.

PMID: 15453262 [PubMed - indexed for MEDLINE]

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