論文 - 詳細
| RRC ID | 72972 |
|---|---|
| 著者 | Koshimura K, Tanaka J, Murakami Y, Kato Y. |
| タイトル | Enhancement of neuronal survival by 6R-tetrahydrobiopterin. |
| ジャーナル | Neuroscience |
| Abstract |
Recently, we have reported that 6R-tetrahydrobiopterin activates Ca2+ channels in neuronal cells independently of its cofactor activities. Several reports indicate that depolarization-induced activation of Ca2+ channels enhances neuronal survival. Here, we investigated the effects of 6R-tetrahydrobiopterin on survival of differentiated PC12 cells. Depletion of serum and nerve growth factor caused cell death, which was prevented by high potassium. 6R-Tetrahydrobiopterin also prevented death of PC12 cells cultured without serum and nerve growth factor in a dose-related manner at physiological concentrations (1-100 microM). However, surviving cells cultured with 6R-tetrahydrobiopterin showed undifferentiated form. 6S-Tetrahydrobiopterin, a diastereoisomer of 6R-tetrahydrobiopterin, also had a cell-surviving effect, but it was less potent as compared with that of 6R-tetrahydrobiopterin. The cell-surviving effect of 6R-tetrahydrobiopterin was eliminated by a Ca2+ channel blocker, but persisted in the presence of an inhibitor for tyrosine hydroxylase, dopamine, L-DOPA, an inhibitor for nitric oxide synthase and a nitric oxide generator. The effect of 6R-tetrahydrobiopterin was mimicked by a cyclic-AMP analogue and inhibited by an inhibitor for protein kinase A. Ca2+ channel activity was preserved but dopamine-releasing activity was disturbed in surviving cells cultured with 6R-tetrahydrobiopterin. 6R-Tetrahydrobiopterin had no effect on mitogen-activated protein kinase. These findings suggest that, independently of its cofactor activities and mitogen-activated protein kinase cascade, 6R-tetrahydrobiopterin enhances survival of PC12 cells by activating Ca2+ channels via the cyclic-AMP-protein kinase A pathway, but that 6R-tetrahydrobiopterin does not preserve neuronal character induced by nerve growth factor. |
| 巻・号 | 88(2) |
| ページ | 561-9 |
| 公開日 | 1999-1-1 |
| DOI | 10.1016/s0306-4522(98)00199-7 |
| PII | S0306452298001997 |
| PMID | 10197775 |
| MeSH | Animals Antioxidants / pharmacology* Biopterin / analogs & derivatives* Biopterin / pharmacology Calcium / pharmacokinetics Calcium Channel Blockers / pharmacology Calcium Channels / physiology Calcium Radioisotopes Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Differentiation / drug effects Cell Survival / drug effects Cyclic AMP / analogs & derivatives Cyclic AMP / pharmacology Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Inhibitors / pharmacology NG-Nitroarginine Methyl Ester / pharmacology Neurons / chemistry Neurons / cytology* Neurons / enzymology Nicardipine / pharmacology Nitric Oxide Synthase / metabolism PC12 Cells Potassium Chloride / pharmacology Rats Thionucleotides / pharmacology |
| IF | 3.056 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |