cAMP inhibits cytokine-induced biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells

Masatsugu Ohtsuki, Hiroaki Shiraishi, Taiya Kato, Risa Kuroda, Masahiro Tazawa, Chiho Sumi-Ichinose, Shin Tada, Yasutoshi Udagawa, Mitsuyasu Itoh, Hitoshi Hishida, Hiroshi Ichinose, Toshiharu Nagatsu, Yasumichi Hagino, Takahide Nomura

研究成果: Article

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We studied the effects of cAMP on cytokine (interferon-γ plus tumor necrosis factor-α)-induced stimulation of tetrahydrobiopterin (BH4) synthesis in human umbilical vein endothelial cells (HUVEC). The cytokine mixture caused a marked increase in the biosynthesis and release of BH4 by HUVEC. Dibutyryl-cAMP produced a dose-dependent inhibition of this cytokine-induced stimulation of synthesis and release of BH4 by these cells. 8-Bromo-cAMP also caused a significant inhibition, although the effects were less marked than those of dibutyryl-cAMP. Both forskolin and the stable analog of prostacyclin, iloprost, caused cAMP accumulation and a concomitant diminution of the cytokine-induced BH4 synthesis in HUVEC. Dibutyryl-cAMP and iloprost also significantly inhibited the cytokine-induced stimulation of GTP cyclohydrolase I (GCHI) activity and mRNA production. We concluded that the suppression by the cAMP messenger system of cytokine-induced stimulation of synthesis and release of BH4 by HUVEC can be attributed to the inhibition of the activity of GCHI, the rate-limiting enzyme in BH4 biosynthetic pathway, in HUVEC. The data also suggest that the cAMP-mediated reduction in the GCHI mRNA level may at least partially explain the decline in GCHI activity. It is reasoned that under inflammatory conditions, cAMP-elevating agents such as prostacyclin exert regulatory effects on circulation by inhibiting cytokine-induced synthesis and release of BH4 by HUVEC.

元の言語English
ページ(範囲)2187-2198
ページ数12
ジャーナルLife Sciences
70
発行部数18
DOI
出版物ステータスPublished - 22-03-2002

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

これを引用

Ohtsuki, M., Shiraishi, H., Kato, T., Kuroda, R., Tazawa, M., Sumi-Ichinose, C., Tada, S., Udagawa, Y., Itoh, M., Hishida, H., Ichinose, H., Nagatsu, T., Hagino, Y., & Nomura, T. (2002). cAMP inhibits cytokine-induced biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells. Life Sciences, 70(18), 2187-2198. https://doi.org/10.1016/S0024-3205(02)01503-5