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- 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细胞功能影响的新发现。1)硫氧还蛋白还原酶（DNCB）抑制剂通过caspase激活导致InPC12细胞凋亡。含s -亚硝基半胱氨酸的NO化合物可抑制caspase的激活和细胞凋亡。2) s -亚硝基半胱氨酸刺激大鼠脑切片去甲肾上腺素释放，而其他NO化合物无刺激作用。s -亚硝基半胱氨酸在调节去甲肾上腺素释放的蛋白质上起巯基作用。3) s -亚硝基半胱氨酸修饰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Ca2+通道的活性。4) s -亚硝基半胱氨酸调控PC12细胞中含有synaptophysin和SNAP-25的囊泡易位。5) s -亚硝基半胱氨酸与gtp结合蛋白如Gi/Go中的半胱氨酸残基反应，引起百日毒对adp核糖基化的抑制。6)胞质磷脂酶A2抑制剂和s -亚硝基半胱氨酸可抑制花生四烯酸在PC12细胞中的释放，而其他NO类化合物则无抑制作用。这些发现表明了s -亚硝基半胱氨酸对神经元细胞功能的调节作用。

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.