Reduced nitric oxide metabolites in CSF of patients with tetrahydrobiopterin deficiency

被引：27

作者：

Zorzi, G ^{[1
]}

Thöny, B ^{[1
]}

Blau, N ^{[1
]}

机构：

[1] Univ Childrens Hosp Zurich, Div Clin Chem & Biochem, CH-8032 Zurich, Switzerland

来源：

JOURNAL OF NEUROCHEMISTRY | 2002年 / 80卷 / 02期

关键词：

dihydropteridine; neurotoxicity; nitric oxide synthase; peroxynitrite; 6-pyruvoyi-tetrahydropterin; sepiapterin;

D O I：

10.1046/j.0022-3042.2001.00710.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We investigated CSF concentrations of nitrite and nitrate as indicators of nitric oxide (NO) production in patients with tetrahydrobiopterin (BH4) deficiencies. Patients with 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase and dihydropteridine reductase deficiencies exhibited decreased CSF nitrite + nitrate levels compared with healthy control subjects. Reduced levels of nitrite + nitrate were not influenced by oral administration of 2.5-5.0 mg/kg tetrahydrobiopterin. Our data indicate impaired NO synthase function in patients with BH4 deficiency and suggest possible involvement in the neuronal cell dysfunction.

引用

页码：362 / 364

页数：3

共 12 条

[1] Tetrahydrobiopterin deficiencies without hyperphenylalaninemia:: Diagnosis and genetics of DOPA-responsive dystonia and sepiapterin reductase deficiency [J].

Blau, N ;

Bonafé, L ;

Thöny, B .

MOLECULAR GENETICS AND METABOLISM, 2001, 74 (1-2) :172-185

[2]

Blau N, 2001, METABOLIC MOL BASES, P1725

[3] Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia [J].

Bonafé, L ;

Thöny, B ;

Penzien, JM ;

Czarnecki, B ;

Blau, N .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (02) :269-277

[4]

Brand MP, 1996, BRAIN RES, V735, P169

[5] Stimulation of the brain NO/cyclic GMP pathway by peripheral administration of tetrahydrobiopterin in the hph-1 mouse [J].

Canevari, L ;

Land, JM ;

Clark, JB ;

Heales, SJR .

JOURNAL OF NEUROCHEMISTRY, 1999, 73 (06) :2563-2568

[6] Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats [J].

Cosentino, F ;

Patton, S ;

d'Uscio, LV ;

Werner, ER ;

Werner-Felmayer, G ;

Moreau, P ;

Malinski, T ;

Lüscher, TF .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) :1530-1537

[7] Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency [J].

Dudesek, A ;

Röschinger, W ;

Muntau, AC ;

Seidel, J ;

Leupold, D ;

Thöny, B ;

Blau, N .

EUROPEAN JOURNAL OF PEDIATRICS, 2001, 160 (05) :267-276

[8] Cerebrospinal fluid nitrite plus nitrate correlates with tetrahydrobiopterin concentration [J].

Heales, SJR ;

Canevari, L ;

Brand, MP ;

Clark, JB ;

Land, JM ;

Hyland, K .

JOURNAL OF INHERITED METABOLIC DISEASE, 1999, 22 (03) :221-223

[9] TETRAHYDROBIOPTERIN AND QUINONOID DIHYDROBIOPTERIN CONCENTRATIONS IN CSF FROM PATIENTS WITH DIHYDROPTERIDINE REDUCTASE DEFICIENCY [J].

HYLAND, K ;

HEALES, SJR .

JOURNAL OF INHERITED METABOLIC DISEASE, 1993, 16 (03) :608-610

[10]

Jones CL, 2001, PTERIDINES, V12, P52

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