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Titolo:
Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase
Autore:
Ishii, M; Shimizu, S; Nagai, T; Shiota, K; Kiuchi, Y; Yamamoto, T;
Indirizzi:
Showa Univ, Sch Pharmaceut Sci, Dept Clin Pharm, Shinagawa Ku, Tokyo 1428555, Japan Showa Univ Tokyo Japan 1428555 Pharm, Shinagawa Ku, Tokyo 1428555, Japan Showa Univ, Sch Pharmaceut Sci, Dept Pathophysiol, Shinagawa Ku, Tokyo 1428555, Japan Showa Univ Tokyo Japan 1428555 ysiol, Shinagawa Ku, Tokyo 1428555, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
fascicolo: 1, volume: 33, anno: 2001,
pagine: 65 - 73
SICI:
1357-2725(200101)33:1<65:SOTSIB>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; HUMAN ENDOTHELIAL-CELLS; GTP CYCLOHYDROLASE-I; RAT AORTA; RELEASE ACCOUNTS; RELAXING FACTOR; MESSENGER-RNA; PROTEIN; AMELIORATION;
Keywords:
insulin; tetrahydrobiopterin; GTP cyclohydrolase I; phosphatidylinositol 3-kinase; endothelial cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Yamamoto, T Showa Univ, Sch Pharmaceut Sci, Dept Clin Pharm, Shinagawa Ku,1-5-8 Hatanodai, Tokyo 1428555, Japan Showa Univ 1-5-8 Hatanodai Tokyo Japan 1428555 1428555, Japan
Citazione:
M. Ishii et al., "Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase", INT J BIO C, 33(1), 2001, pp. 65-73

Abstract

Although we recently showed that insulin increases the intracellular concentration of tetrahydrobiopterin (BH4), which is one of the cofactors of nitric oxide (NO) synthase, the mechanism of the effect was not elucidated. Inthe present study, we examined the signaling pathway of the stimulation ofBH4 synthesis by insulin in mouse brain microvascular endothelial cells. Extracellular and intracellular BH4 levels were determined as biopterin by using reversed-phase high performance liquid chromatography with fluorometric detection. Measurement of the level of mRNA for GTP cyclohydrolase I (GTPCH), which is the rate-limiting enzyme for de novo BH4 synthesis, was performed by reverse transcription-polymerase chain reaction (RT-PCR). Addition of insulin to endothelial cells caused an increase of not only the intracellular but also the extracellular BH4 level in a time- and a concentration-dependent manner. Insulin also induced an increase of the level of GTPCH mRNA. Moreover, 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, inhibited the insulin-induced enhancement of BH4 synthesis. The increase in the BH4 level and the induction of GTPCH mRNA by insulin were reduced by wortmannin and LY294002, which are both phosphatidylinositol 3-kinase (PI3-kinase)inhibitors. These results suggest that insulin stimulates BH4 synthesis through the de novo synthetic pathway involving induction of GTPCH, and that the signaling pathway involves the activation of PI3-kinase. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 01:48:39