Zhang W Y, Gotoh T, Oyadomari S, Mori M
Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo 2-2-1, 860-0811, Kumamoto, Japan.
Brain Res Mol Brain Res. 2000 Nov 10;83(1-2):1-8. doi: 10.1016/s0169-328x(00)00154-6.
Nitric oxide (NO) is involved in many physiological and pathological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS), and the citrulline generated as a by-product can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) via the citrulline-NO cycle. When neuronal PC12 cells differentiated with nerve growth factor were treated with interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), iNOS and AS mRNAs and proteins were markedly induced, with AL mRNA and protein being weakly induced. Cationic amino acid transporter-1 and -2 were not induced. IFNgamma or TNFalpha alone was ineffective. A large amount of NO (190 microM NO(2)(-) plus NO(3)(-) in culture medium in 24 h) was produced from arginine by cytokine-stimulated cells, and arginine could be replaced by citrulline. iNOS induction and NO production were attenuated by dexamethasone and dibutyryl cAMP and even more strongly so when combined. Therefore, a large amount of NO is produced in cytokine-stimulated PC12 cells following to induction of iNOS and citrulline-arginine recycling is important for NO production.
一氧化氮（NO）参与大脑中的许多生理和病理过程。NO由一氧化氮合酶（NOS）从精氨酸合成，作为副产物生成的瓜氨酸可通过瓜氨酸-NO循环，由精氨琥珀酸合成酶（AS）和精氨琥珀酸裂解酶（AL）再循环为精氨酸。当用神经生长因子分化的神经元PC12细胞用γ-干扰素（IFNγ）和肿瘤坏死因子-α（TNFα）处理时，诱导型一氧化氮合酶（iNOS）和AS的mRNA及蛋白显著增加，而AL的mRNA和蛋白诱导较弱。阳离子氨基酸转运体-1和-2未被诱导。单独的IFNγ或TNFα无效。细胞因子刺激的细胞从精氨酸产生大量NO（24小时内培养基中190微摩尔NO2-加NO3-），精氨酸可用瓜氨酸替代。地塞米松和二丁酰环磷腺苷（dibutyryl cAMP）可减弱iNOS的诱导和NO的产生，两者联合时作用更强。因此，细胞因子刺激的PC12细胞在诱导iNOS后产生大量NO，瓜氨酸-精氨酸循环对NO的产生很重要。
