Abstract |
We investigated for the first time the effect of lipopolysaccharide and the signal transduction pathway on the biosynthesis of tetrahydrobiopterin [(6R-L-erythro-1',2'-dihydroxypropyl) -2-amino-4-hydroxy-5,6,7,8- tetrahydropteridine], the cofactor for the enzymatic hydroxylation of the aromatic amino acids, in the murine neuroblastoma cell line N1E-115, which synthesizes tetrahydrobiopterin constitutively. Activation of N1E-115 cells with 1 microgram/ml lipopolysaccharide resulted in statistically significant increases in both intracellular tetrahydrobiopterin contents and the activity (Vmax) of GTP cyclohydrolase I, a rate-limiting enzyme in tetrahydrobiopterin de novo biosynthesis. Following simultaneous addition of the inhibitors of protein tyrosine kinases and GTP-binding proteins into serum-free culture media with lipopolysaccharide, we analyzed the transduction pathway of lipopolysaccharide signal toward the tetrahydrobiopterin biosynthetic system in N1E-115 cells. Our data indicate the following conclusions: (a) Protein tyrosine kinase systems are involved in mediating lipopoly-saccharide signal to tetrahydrobiopterin production, and (b) there may be a cross-talk between GTP-binding protein and the protein tyrosine kinase system in mediating lipopolysaccharide signal. These observations suggest that a neuronal cell such as N1E-115, which barely expresses CD14 on its cell surface, responds to lipopolysaccharide like macrophages and monocytes in the absence of soluble CD14.
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Authors | A Ota, S Yoshida, T Nomura, S Matsui, Y Hagino, K Umezawa, S Katoh, T Nagatsu |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 67
Issue 6
Pg. 2540-8
(Dec 1996)
ISSN: 0022-3042 [Print] England |
PMID | 8931488
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Antioxidants
- Benzoquinones
- Enzyme Inhibitors
- Hydroquinones
- Lactams, Macrocyclic
- Lipopolysaccharides
- Quinones
- Ribonucleosides
- Rifabutin
- Biopterin
- herbimycin
- oxanosine
- GTP Cyclohydrolase
- sapropterin
- erbstatin
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Topics |
- Animals
- Anti-Bacterial Agents
(pharmacology)
- Antioxidants
(metabolism)
- Benzoquinones
- Biopterin
(analogs & derivatives, biosynthesis)
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- GTP Cyclohydrolase
(metabolism)
- Hydroquinones
(pharmacology)
- Lactams, Macrocyclic
- Lipopolysaccharides
(pharmacology)
- Mice
- Neuroblastoma
- Quinones
(pharmacology)
- Ribonucleosides
(pharmacology)
- Rifabutin
(analogs & derivatives)
- Signal Transduction
(drug effects, physiology)
- Tumor Cells, Cultured
(drug effects, enzymology, metabolism)
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