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Titolo:
Catecholamines and serotonin are differently regulated by tetrahydrobiopterin - A study from 6-pyruvoyltetrahydropterin synthase knockout mice
Autore:
Sumi-Ichinose, C; Urano, F; Kuroda, R; Ohye, T; Kojima, M; Tazawa, M; Shiraishi, H; Hagino, Y; Nagatsu, T; Nomura, T; Ichinose, H;
Indirizzi:
Fujita Hlth Univ, Inst Comprehens Med Sci, Div Mol Genet, Toyoake, Aichi 4701192, Japan Fujita Hlth Univ Toyoake Aichi Japan 4701192 oyoake, Aichi 4701192, Japan Fujita Hlth Univ, Sch Med, Dept Pharmacol, Toyoake, Aichi 4701192, Japan Fujita Hlth Univ Toyoake Aichi Japan 4701192 oyoake, Aichi 4701192, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 44, volume: 276, anno: 2001,
pagine: 41150 - 41160
SICI:
0021-9258(20011102)276:44<41150:CASADR>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; TYROSINE-HYDROXYLASE ACTIVITY; DOPA-RESPONSIVE DYSTONIA; MOUSE FETAL DEVELOPMENT; TARGETED DISRUPTION; INTERFERON-GAMMA; GENE; STRIATUM; COFACTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Ichinose, H Fujita Hlth Univ, Inst Comprehens Med Sci, Div Mol Genet, Toyoake, Aichi 4701192, Japan Fujita Hlth Univ Toyoake Aichi Japan 4701192 i 4701192, Japan
Citazione:
C. Sumi-Ichinose et al., "Catecholamines and serotonin are differently regulated by tetrahydrobiopterin - A study from 6-pyruvoyltetrahydropterin synthase knockout mice", J BIOL CHEM, 276(44), 2001, pp. 41150-41160

Abstract

(6R)-L-erythro-5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH), tryptophan hydroxylase, phenylalanine hydroxylase, and nitric-oxide synthase. These enzymes synthesize neurotransmitters, e.g. catecholamines, serotonin, and nitric oxide (NO). We established mice unable to synthesize BH4 by disruption of the 6-pyruvoyltetrahydropterinsynthase gene, the encoded protein of which catalyzes the second step of BH4 biosynthesis. Homozygous mice were born at the almost expected Mendelianratio, but died within 48 h after birth. In the brain of homozygous mutantneonates, levels of biopterin, catecholamines, and serotonin were extremely low. The number of TH molecules was highly dependent on the intracellularconcentration of BH4 at nerve terminals. Alteration of the TH protein level by modulation of the BH4 content is a novel regulatory mechanism. Our data showing that catecholaminergic, serotonergic, and NO systems were differently affected by BH4 starvation suggest the possible involvement of BH4 synthesis in the etiology of monoamine-based neurological and neuropsychiatricdisorders.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 11:40:03