Enhanced expression of GTP cyclohydrolase I in V-1-overexpressing PC12D cells

Takahiro Suzuki, Hidehito Inagaki, Tohru Yamakuni, Toshiharu Nagatsu, Hiroshi Ichinose

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13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)962-968
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume293
Issue number3
DOIs
Publication statusPublished - 01-01-2002

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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