J Korean Neurol Assoc.  2001 Sep;19(5):514-519.

Effects of Cofactor Tetrahydrobiopterin and Deletions on the Regulatory Domain of Tyrosine Hydroxylase on the Expression of Tyrosine Hydroxylase

• Cho YW
• Yi SD
• Lim JK
• Lee H
• Kim YS
• Lee U
• Lee YJ

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 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)

Keyword

Parkinson's disease; Tyrosine hydroxylase; Regulatory domain; Phosphorylation; Cofactor; Expression

MeSH Terms

Dopamine
Models, Animal
Neurons
Parkinson Disease
Phosphorylation
Protein Stability
RNA, Messenger
Tyrosine 3-Monooxygenase*
Tyrosine*
United Nations
Dopamine
RNA, Messenger
Tyrosine
Tyrosine 3-Monooxygenase