Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, PR China.
Neurochem Int. 2010 Mar;56(4):561-8. doi: 10.1016/j.neuint.2009.12.019. Epub 2010 Jan 11.
Astrocytes play a key role in regulating aspects of inflammation in the central nervous system. It was observed that nNOS had located in the nucleus of cultured cerebral cortical astrocytes of 7 days. In the present study, we found that carboxy-terminal PDZ ligand of nNOS (CAPON) mainly located in the nucleus of astrocytes stimulated with NO donor sodium nitroprusside (SNP) or GSNO or N-methyl-d-aspartate (NMDA) receptor agonist-NMDA. However, originally, it was localized mostly in the cytoplasm of normal astrocytes. Immunocytochemistry showed that nNOS was co-localized with CAPON in the nucleus of astrocytes stimulated with SNP. In addition to the nuclear localization, treatment with SNP increased the mRNA and protein expression of CAPON. When SNP was removed from media, CAPON accumulated in nucleus transported back to cytoplasm. MK801, an inhibitor of NMDA receptor, was able to reverse the nuclear localization of CAPON resulted from SNP, suggesting that there is a functional relationship of NO with NMDA receptor in the regulation of the nuclear localization of CAPON. These findings provide a new insight in the understanding of the physical and pathological significances of CAPON/nNOS/NMDA receptor.
星形胶质细胞在调节中枢神经系统炎症方面起着关键作用。有研究观察到，培养的 7 天大脑皮质星形胶质细胞中的 nNOS 位于细胞核内。在本研究中，我们发现 nNOS 的羧基端 PDZ 配体（CAPON）主要位于被一氧化氮供体硝普钠（SNP）、S-亚硝基谷胱甘肽（GSNO）或 N-甲基-D-天冬氨酸（NMDA）受体激动剂-NMDA 刺激的星形胶质细胞的细胞核内。然而，正常星形胶质细胞中 CAPON 主要位于细胞质内。免疫细胞化学显示，在 SNP 刺激的星形胶质细胞的细胞核内，nNOS 与 CAPON 共定位。除了核定位外，SNP 处理还增加了 CAPON 的 mRNA 和蛋白表达。当从培养基中去除 SNP 时，CAPON 会在细胞核内积累并被转运回细胞质。NMDA 受体抑制剂 MK801 能够逆转 SNP 导致的 CAPON 的核定位，这表明在调节 CAPON/NMDA 受体的核定位中，NO 与 NMDA 受体之间存在功能关系。这些发现为理解 CAPON/nNOS/NMDA 受体在生理和病理意义上提供了新的认识。
