Regulation of Neuregulin Expression in the Injured Rat Brain and Cultured Astrocytes
Regulation of Neuregulin Expression in the Injured Rat Brain and Cultured Astrocytes
复制标题
DOI：
10.1523/jneurosci.21-04-01257.2001
复制
发表时间：
2001-02
期刊：
影响因子：
--
通讯作者：
Y. Tokita;H. Keino;F. Matsui;S. Aono;H. Ishiguro;S. Higashiyama;A. Oohira
中科院分区：
文献类型：
--
作者：
Y. Tokita;H. Keino;F. Matsui;S. Aono;H. Ishiguro;S. Higashiyama;A. Oohira
在这份报告中，我们调查是否反应性星形胶质细胞产生神经调节蛋白（胶质细胞生长因子2/heregulin/乙酰胆碱受体诱导活性或神经分化因子）及其假定的受体，ErbB 2和ErbB 3酪氨酸激酶，在体内受损的中枢神经系统。在成年大鼠大脑皮层损伤后4 d，在损伤部位的星形胶质细胞上检测到抗神经调节蛋白、抗ErbB 2和抗ErbB 3抗体的显著免疫反应性。为了阐明星形胶质细胞中神经调节蛋白表达上调的机制，用某些试剂（包括毛喉素）处理原代培养的星形胶质细胞，已知所述试剂升高细胞内cAMP水平并诱导星形胶质细胞中显著的形态学变化。Western印迹分析表明，一个52 kDa的跨膜形式的神经调节蛋白的表达增强培养的星形胶质细胞给药后的毛喉素。在用毛喉素处理的星形胶质细胞中也观察到胶质细胞酸性蛋白的上调。相比之下，蛋白激酶C的失活，因为长期治疗与佛波酯12-O-十四烷酰基佛波13-乙酸酯下调的52 kDa亚型的表达，虽然其他剪接变异体的表观分子大小为65和60 kDa的上调。这些结果表明，在损伤部位的神经调节蛋白的表达的增强诱导，至少部分，通过升高细胞内cAMP水平和/或蛋白激酶C信号通路。神经调节蛋白在反应性星形胶质细胞上的表达可能刺激它们的增殖，并支持体内皮层脑创伤周围神经元的存活。
In this report, we investigated whether reactive astrocytes produce neuregulins (glial growth factor 2/heregulin/acetylcholine receptor-inducing activity or neu differentiation factor) and its putative receptors, ErbB2 and ErbB3 tyrosine kinases, in the injured CNS in vivo. Significant immunoreactivities with anti-neuregulin, anti-ErbB2, and anti-ErbB3 antibodies were detected on astrocytes at the injured site 4 d after injury to the adult rat cerebral cortex. To elucidate the mechanisms for the upregulation of neuregulin expression in astrocytes, primary cultured astrocytes were treated with certain reagents, including forskolin, that are known to elevate the intracellular level of cAMP and induce marked morphological changes in astrocytes. Western blot analysis showed that the expression of a 52 kDa membrane-spanning form of a neuregulin protein was enhanced in cultured astrocytes after administration of forskolin. The upregulation of glial fibrillary acidic protein was also observed in astrocytes treated with forskolin. In contrast, inactivation of protein kinase C because of chronic treatment with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate downregulated the expression of the 52 kDa isoform, although other splice variants with apparent molecular sizes of 65 and 60 kDa were upregulated. These results suggest that the enhancement of neuregulin expression at injured sites is induced, at least in part, by elevation in intracellular cAMP levels and/or a protein kinase C signaling pathway. The neuregulin expressed on reactive astrocytes may stimulate their proliferation and support the survival of neurons surrounding cortical brain wounds in vivo.