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Regulation of neuronal cell functions by S-nitroso-cysteine

S-亚硝基半胱氨酸调节神经细胞功能

基本信息

批准号：
11680749
负责人：
MURAYAMA Toshihiko
金额：
$ 2.11万
依托单位：
Chiba University (2000)Hokkaido University (1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680749/
关键词：
nitric oxide NO radical S-nitroso-cysteine neuronal cells phospholipase A2 arachidonic acid apoptosis caspase

项目摘要

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.

此前，我们提出了一种新的信号转导机制[NO自由基-S-亚硝基-硫醇形成-蛋白质的S-亚硝基化]。在本研究中，我们获得了一些关于 S-亚硝基-半胱氨酸对神经元细胞功能影响的新发现。 1) 在PC12细胞中，硫氧还蛋白还原酶(DNCB)抑制剂通过半胱天冬酶激活引起细胞凋亡。用包括S-亚硝基-半胱氨酸在内的NO化合物处理可抑制半胱天冬酶激活和细胞凋亡。 2) S-亚硝基-半胱氨酸，但不是其他一氧化氮化合物，刺激大鼠脑切片中去甲肾上腺素的释放。 S-亚硝基半胱氨酸作为调节去甲肾上腺素释放的蛋白质的巯基剂。 3) S-亚硝基-半胱氨酸改变咖啡因敏感受体上巯基的氧化状态，以可逆的方式调节 PC12 细胞中的 Ca2+ 通道活性。 4) S-亚硝基-半胱氨酸调节 PC12 细胞中含有突触素和 SNAP-25 的囊泡的易位。 5) S-亚硝基-半胱氨酸与 GTP 结合蛋白（例如 Gi/Go）中的半胱氨酸残基反应，导致百日咳毒素抑制 ADP-核糖基化。 6) PC12 细胞中花生四烯酸的释放受到胞质磷脂酶 A2 抑制剂和 S-亚硝基半胱氨酸的抑制，但不受其他 NO 化合物的抑制。这些发现表明 S-亚硝基-半胱氨酸对神经细胞功能的调节。