Regulations and pathophysiological significance of the biosynthesis of tetrahydrobiopterin in human endothelial cells

Hiroaki Shiraishi, Masatsugu Ohtsuki, Chiho Sumi-Ichinose, Takahide Nomura

Research output: Contribution to journalArticle

Abstract

Tetrahydrobiopterin(BH4) serves as an essential cofactor for the biosynthesis of nitric oxide (NO). BH4 is de novo synthesized from GTP and GTP cyclohydrolase I(GCH I) is the rate-limiting enzyme in the biosynthesis of BH4. Under inflammatory conditions, it is reported that endothelial cells release large amount of BH4. In this study, we examined the regulation mechanism of the biosynthesis of BH4 in human umbilical vein endothelial cells(HUVEC). Prostacyclin and forskolin, reagents of stimulation of cAMP signaling cascade, reduced cytokine induced biosynthesis of BH4 through the inhibition of expression of GCH I mRNA. On the other hand, stimulations of NO-cGmp signaling pathway inhibited GCH I activities through the post translational modification of GCH I enzyme. Both two signaling cascade lead to vasodilation. It is suggested that the biosynthesis of BH4 can be regulated by negative feed back regulation systems between endothelium and smooth muscle cells to prevent over stimulated vasodilation.

Original languageEnglish
JournalFolia Pharmacologica Japonica
Volume120
Issue numberSUPPL. 1
Publication statusPublished - 17-12-2002

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GTP Cyclohydrolase
Endothelial Cells
Vasodilation
Nitric Oxide
Human Umbilical Vein Endothelial Cells
Colforsin
Epoprostenol
Enzymes
Post Translational Protein Processing
Guanosine Triphosphate
Smooth Muscle Myocytes
Endothelium
Cytokines
Messenger RNA
sapropterin

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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abstract = "Tetrahydrobiopterin(BH4) serves as an essential cofactor for the biosynthesis of nitric oxide (NO). BH4 is de novo synthesized from GTP and GTP cyclohydrolase I(GCH I) is the rate-limiting enzyme in the biosynthesis of BH4. Under inflammatory conditions, it is reported that endothelial cells release large amount of BH4. In this study, we examined the regulation mechanism of the biosynthesis of BH4 in human umbilical vein endothelial cells(HUVEC). Prostacyclin and forskolin, reagents of stimulation of cAMP signaling cascade, reduced cytokine induced biosynthesis of BH4 through the inhibition of expression of GCH I mRNA. On the other hand, stimulations of NO-cGmp signaling pathway inhibited GCH I activities through the post translational modification of GCH I enzyme. Both two signaling cascade lead to vasodilation. It is suggested that the biosynthesis of BH4 can be regulated by negative feed back regulation systems between endothelium and smooth muscle cells to prevent over stimulated vasodilation.",
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Regulations and pathophysiological significance of the biosynthesis of tetrahydrobiopterin in human endothelial cells. / Shiraishi, Hiroaki; Ohtsuki, Masatsugu; Sumi-Ichinose, Chiho; Nomura, Takahide.

In: Folia Pharmacologica Japonica, Vol. 120, No. SUPPL. 1, 17.12.2002.

Research output: Contribution to journalArticle

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AU - Sumi-Ichinose, Chiho

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