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Journal of the Korean Neurological Association 2001;19(5): 514-519.
Tetrahydrobiopterin과 Tyrosine Hydroxylase 조절부위의 인위적 변이가 Tyrosine Hydroxylase의 발현에 미치는 영향
조용원, 조용원이이상도이임정근이이이형이김용식*이언†이영재†
계명대학교 의과대학 신경과학교실,서울대학교 의과대학 약리학교실*,가천의대 신경과학연구소†
"Effects of Cofactor Tetrahydrobiopterin and Deletions on the Regulatory Domain of Tyrosine Hydroxylase on the Expression of Tyrosine Hydroxylase"
Yong-won Cho, M.D., Sang-Doe Yi, M.D., Jung-Kun Lim, M.D.,Hyung Lee, M.D., Yong-Sik Kim, M.D.*, Uhn Lee, M.D.†, Young-Jae Lee, Ph.D.†
Department of Neurology, Keimyung University, Department of Pharmacology, Seoul National University*,Neuroscience Research Institute, Gachon Medical School
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 hydrox-ylase (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 tremen-dous effect on the translation and/or protein stability, but a small effect on the mRNA level. J Korean Neurol Assoc 19(5):514~519, 2001 Key Words : Parkinson’s disease, Tyrosine hydroxylase, Regulatory domain, Phosphorylation, Cofactor, Expression"