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Involvement of superoxide in excitotoxicity & DNA fragmentation in straiatal vulnerability in mice after treatment with the mitochondrial toxin, 3-NP

Authors
 Gyung W. Kim  ;  Pak H. Chan 
Citation
 JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol.22(7) : 798-809, 2002 
Journal Title
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
ISSN
 0271-678X 
Issue Date
2002
Keywords
Superoxide ; Excitotoxicity ; 3-Nitropropionic acid ; Striatal vulnerability ; Huntington’s disease
Abstract
Oxidative stress and excitotoxicity have been implicated in selective striatal vulnerability caused by the mitochondrial toxin, 3-nitropropionic acid (3-NP), which may simulate Huntington's disease in animals and humans. The detailed mechanism of the role of superoxide in striatal vulnerability induced by 3-NP is still unknown. The authors investigated oxidative cellular injury and DNA fragmentation after systemic 3-NP injection in wild-type (Wt) mice and mutant mice with a deficiency in manganese superoxide dismutase (MnSOD; Sod2 -/+). Furthermore, they investigated the effects of decortication after 3-NP treatment in Sod2 -/+ mice, and copper/zinc SOD (CuZnSOD) treatment in recently developed Sod2 -/+ mice that overexpress CuZnSOD (SOD1 +/- / Sod2 -/+ mice). Oxidized hydroethidine, 8-hydroxyguanosine immunoreactivity, and nitrotyrosine immunoreactivity were increased in the Sod2 -/+ mice compared with the Wt mice after 3-NP treatment (P < 0.001). Decortication completely abolished oxidative striatal damage after 3-NP treatment in the Sod2 -/+ mice. Increased CuZnSOD attenuated DNA fragmentation and striatal lesion volume after 3-NP treatment in the Sod2 -/+ mice (P < 0.001). These data suggest that production of superoxide may be a critical step to excitotoxicity and subsequent DNA fragmentation in selective striatal vulnerability after 3-NP treatment.
Files in This Item:
T200202290.pdf Download
DOI
10.1097/00004647-200207000-00005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143422
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