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Immobilization stress causes increases in tetrahydrobiopterin, dopamine, and neuromelanin and oxidative damage in the nigrostriatal system

Authors
 Sung Tae Kim  ;  Ji Hyun Choi  ;  Jin Woo Chang  ;  Seong Who Kim  ;  Onyou Hwang 
Citation
 JOURNAL OF NEUROCHEMISTRY, Vol.95(1) : 89-98, 2005 
Journal Title
JOURNAL OF NEUROCHEMISTRY
ISSN
 0022-3042 
Issue Date
2005
MeSH
Animals ; Biopterin/analogs & derivatives* ; Biopterin/antagonists & inhibitors ; Biopterin/metabolism ; Brain/metabolism* ; Brain/pathology* ; Catalase/metabolism ; Corpus Striatum/metabolism ; Corpus Striatum/pathology ; Dopamine/metabolism* ; Enzyme Inhibitors/pharmacology ; Hypoxanthines/pharmacology ; Male ; Melanins/metabolism* ; Mice ; Mice, Inbred ICR ; Nerve Degeneration/etiology ; Nerve Degeneration/pathology ; Nerve Fibers/pathology ; Oxidative Stress* ; Restraint, Physical* ; Stress, Physiological/complications ; Stress, Physiological/etiology ; Stress, Physiological/metabolism* ; Substantia Nigra/metabolism ; Substantia Nigra/pathology ; Superoxide Dismutase/metabolism ; Tyrosine 3-Monooxygenase/metabolism
Keywords
dopamine ; immobilization stress ; neuromelanin ; oxidative stress ; Parkinson’s disease ; tetrahydrobiopterin
Abstract
Oxidative stress is believed to contribute to the pathophysiology of Parkinson's disease, in which nigrostriatal dopaminergic (DA) neurons undergo degeneration. Identification of endogenous molecules that contribute to generation of oxidative stress and vulnerability of these cells is critical in understanding the etiology of this disease. Exposure to tetrahydrobiopterin (BH4), the obligatory cofactor for DA synthesis, was observed previously to cause oxidative damage in DA cells. To demonstrate the physiological relevance of this observation, we investigated whether an overproduction of BH4 and DA might actually occur in vivo, and, if it did, whether this might lead to oxidative damage to the nigrostriatal system. Immobilization stress (IMO) elevated BH4 and DA and their synthesizing enzymes, tyrosine hydroxylase and GTP cyclohydrolase I. This was accompanied by elevation of lipid peroxidation and protein-bound quinone, and activities of antioxidant enzymes. These increases in the indices of oxidative stress appeared to be due to increased BH4 synthesis because they were abolished following administration of the BH4 synthesis inhibitor, 2,4-diamino-6-hydroxy-pyrimidine. IMO also caused accumulation of neuromelanin and degeneration of the nigrostriatal system. These results demonstrate that a severe stress can increase BH4 and DA and cause oxidative damages to the DA neurons in vivo, suggesting relevance to Parkinson's disease.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2005.03342.x/abstract
DOI
10.1111/j.1471-4159.2005.03342.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/150944
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