NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington's disease.
Nerve growth factor (NGF)-secreting fibroblasts are able to protect against the Huntington-like striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3-NP). In the present study, we investigated whether the neuroprotective effects of NGF are mediated through antioxidative mechanisms. Rats were grafted in the corpus callosum with NGF[+] or NGF[-] fibroblasts 7 days before administration of 3-NP. The generation of peroxynitrite was evaluated by measuring the striatal levels of 3-nitrotyrosine. NGF significantly decreased the 3-NP induced generation of 3-nitrotyrosine, presumably by decreasing peroxynitrite formation. These findings suggest that NGF might protect against neuronal death by inhibiting the production of nitric oxide or decreasing the levels of superoxide radicals, thereby decreasing the generation of oxidative agents such as peroxynitrite.
Galpern
W R
WR
Neuroregeneration Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02178, USA.
Matthews
R T
RT
Beal
M F
MF
Isacson
O
O
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009414:Nerve Growth Factors; D009574:Nitro Compounds; D011422:Propionates; C002744:3-nitrotyrosine; D014443:Tyrosine; C015392:3-nitropropionic acid