TY - JOUR
T1 - Enhanced expression of GTP cyclohydrolase I in V-1-overexpressing PC12D cells
AU - Suzuki, Takahiro
AU - Inagaki, Hidehito
AU - Yamakuni, Tohru
AU - Nagatsu, Toshiharu
AU - Ichinose, Hiroshi
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Three of the catecholamine-synthesizing enzymes, i.e., tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase, and dopamine β-hydroxylase, were earlier shown to be up-regulated in cloned PC12D cells overexpressing V-1, a cdc10/SWI6 motif-containing protein. GTP cyclohydrolase I (GCH) is the rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin (BH4), known as an essential cofactor for TH; and here we found the increased expression of GCH in V-1-overexpressing clones. Both GCH activity and total biopterin content were highly increased in the V-1 clones; whereas the activity of sepiapterin reductase, enzyme in the final step of the BH4 biosynthesis, was not altered. Biochemical analyses revealed increased levels of GCH protein, mRNA, and transcription in the V-1 clones. Promoter analysis showed increased reporter activity in the construct with 150 bp of the promoter region of the human GCH gene, suggesting the involvement of cAMP-responsive element-mediated transcriptional regulation.
AB - Three of the catecholamine-synthesizing enzymes, i.e., tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase, and dopamine β-hydroxylase, were earlier shown to be up-regulated in cloned PC12D cells overexpressing V-1, a cdc10/SWI6 motif-containing protein. GTP cyclohydrolase I (GCH) is the rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin (BH4), known as an essential cofactor for TH; and here we found the increased expression of GCH in V-1-overexpressing clones. Both GCH activity and total biopterin content were highly increased in the V-1 clones; whereas the activity of sepiapterin reductase, enzyme in the final step of the BH4 biosynthesis, was not altered. Biochemical analyses revealed increased levels of GCH protein, mRNA, and transcription in the V-1 clones. Promoter analysis showed increased reporter activity in the construct with 150 bp of the promoter region of the human GCH gene, suggesting the involvement of cAMP-responsive element-mediated transcriptional regulation.
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U2 - 10.1016/S0006-291X(02)00343-1
DO - 10.1016/S0006-291X(02)00343-1
M3 - Article
C2 - 12051753
AN - SCOPUS:0036290273
VL - 293
SP - 962
EP - 968
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -