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Neuroprotective effect of cyclic GMP against radical‐induced toxicity in cultured spinal motor neurons
Author(s) -
Urushitani Makoto,
Inoue Ryotaku,
Nakamizo Tomoki,
Sawada Hideyuki,
Shibasaki Hiroshi,
Shimohama Shun
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20000815)61:4<443::aid-jnr11>3.0.co;2-w
Subject(s) - cyclic guanosine monophosphate , glutathione , glutamate receptor , neuroprotection , buthionine sulfoximine , chemistry , oxidative stress , toxicity , pharmacology , guanosine , reactive oxygen species , nitric oxide , biochemistry , biology , receptor , enzyme , organic chemistry
We have previously reported that nitric oxide‐related cyclic guanosine‐3′,5′‐monophosphate (GMP) protected spinal nonmotor neurons, but not motor neurons against chronic glutamate‐induced toxicity, which is associated with selective motor neuronal death after glutamate stress. In this report, we investigated the effect of cyclic GMP against reactive oxygen species (ROS)‐induced toxicity in cultured neurons from embryonic rat spinal cords. Pretreatment with a cGMP analogue, 8‐bromoguanosine monophosphate (8br‐cGMP), for 12–24 hours protected both spinal motor neurons and nonmotor neurons against injury induced by either hydrogen peroxide (H 2 O 2 ), or a glutathione depletor, L‐buthionine‐[S,R]‐sulfoximine (BSO). This protective effect was reversed by coadministration with the cGMP‐dependent protein kinase (PKG) inhibitor Arg‐Lys‐Arg‐Ala‐Arg‐Lys‐Glu. Interestingly, when cultures were exposed to BSO for 24 hours to allow irreversible inhibition of glutathione synthesis, 8br‐cGMP protected only nonmotor neurons. Our results indicate that cGMP attenuates oxidative injury to cultured spinal neurons, in a mechanism associated with glutathione synthesis. J. Neurosci. Res. 61:443–448, 2000. © 2000 Wiley‐Liss, Inc.