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Tetrahydrobiopterin과 Tyrosine Hydroxylase 조절부위의 인위적 변이가 Tyrosine Hydroxylase의 발현에 미치는 영향

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Author(s)
조용원이상도임정근이형김용식이언이영재Yong-won ChoSang-Doe YiJung-Kun LimHyung LeeYong-Sik KimUhn LeeYoung-Jae Lee
Keimyung Author(s)
Cho, Yong WonYi, Sang DoLim, Jeong GeunLee, Hyung
Department
Dept. of Neurology (신경과학)
Journal Title
대한신경과학회지
Issued Date
2001
Volume
19
Issue
5
Abstract
Background : For the treatment of Parkinson’s disease, dopamine-producing cells or genes involved in producing dopamine or supporting neurons have been tested to replace conventional chemical therapies. Of these, tyrosine hydroxylase(TH) was the most widely used gene for the therapy. Trials using TH via various vectors yielded behavioral improvements in animal models but the effectiveness did not last long enough. As one of the approaches for solving this problem, the regulation of expression of the protein and mRNA of TH was studied. Methods : Two approaches for a higher and/or more stable expression of TH were pursued. First, the effect of cofactor tetrahydrobiopterin (BH4) on the expression level of TH and second, the effect of deletion which enables TH protein to escape from protease attack, were examined. Results : Cells producing BH4 showed an approximately 10-fold higher TH expression than cells expressing TH alone. When the in vitro modified TH was expressed in NIH-3T3, mutant THs showed elevated protein (17.5~68.6 fold) and mRNA (1.8~4.6 fold) expression levels at a steady state. Conclusions : Results suggest that an addition of BH4 has a more positive effect on mRNA expression levels than protein. However, the deletions seem to have a tremendous effect on the translation and/or protein stability, but a small effect on the mRNA level.
Alternative Title
Effects of Cofactor Tetrahydrobiopterin and Deletions on the Regulatory Domain of Tyrosine Hydroxylase on the Expression of Tyrosine Hydroxylase
Keimyung Author(s)(Kor)
조용원
이상도
임정근
이형
Publisher
School of Medicine
Citation
조용원 et al. (2001). Tetrahydrobiopterin과 Tyrosine Hydroxylase 조절부위의 인위적 변이가 Tyrosine Hydroxylase의 발현에 미치는 영향. 대한신경과학회지, 19(5), 514–519.
Type
Article
ISSN
1225-7044
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/39163
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
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