2000 Fiscal Year Final Research Report Summary
Regulation of neuronal cell functions by S-nitroso-cysteine
| Project/Area Number |
11680749
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Chiba University (2000)
Hokkaido University (1999) |
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Principal Investigator |
MURAYAMA Toshihiko Chiba University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90174317)
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| Project Period (FY) |
1999 – 2000
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| Keywords | nitric oxide / NO radical / S-nitroso-cysteine / neuronal cells / phospholipase A2 / arachidonic acid / apoptosis / caspase |
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| Research Abstract |
Previously, we proposed a new signal transduction mechanism [NO radical-S-nitroso-thiols formation-S-nitrosylation of proteins]. In the present study, we obtained several new findings concerning the effects of S-nitroso-cysteine on neuronal cell functions. 1) InPC12 cells, an inhibitor of thioredoxin reductase (DNCB) caused apoptosis with caspase activation. Treatment with NO compounds including S-nitroso-cysteine inhibited the caspase activation and the apoptosis. 2) S-Nitroso-cysteine, but not other NO compounds, stimulated noradrenaline release from rat brain slices. S-Nitroso-cysteine acted as a sulfhydryl agent on proteins that regulate noradrenaline release. 3) Modification of the oxidation status of the sulfhydryl groups on the caffeine-sensitive receptors by S-nitroso-cysteine regulated Ca2+ channel activity in a reversible manner in PC12 cells. 4) S-Nitroso-cysteine regulated translocation of vesicles containing synaptophysin and SNAP-25 in PC12 cells. 5) S-Nitroso-cysteine reacted with cysteine residues in GTP-binding proteins such as Gi/Go, causing inhibition of ADP-ribosylation by pertussis toxin. 6) Arachidonic acid release from PC12 cells was inhibited by cytosolic phospholipase A2 inhibitors and by S-nitroso-cysteine, but not by other NO compounds. These findings show the regulation of neuronal cell functions by S-nitroso-cysteine.
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[Publications] Onodera, T., Watanabe, R., Tha, T.T, Hayashi, Y., Murayama, T., Okuma, Y., Ono, C., Oketani, Y., Hosokawa, M.and Nomura, Y.: "Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain in the senescence accelerated mouse (SAM)-P10."Jpn.J.Pharmacol.. 83. 312-318 (2000)
Description
「研究成果報告書概要(欧文)」より
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