Yoshida Yasuhiro, Nakano Yoshiteru, Ueno Susumu, Liu Jiqin, Fueta Yukiko, Ishidao Toru, Kunugita Naoki, Yanagihara Nobuyuki, Sugiura Tsutomu, Hori Hajime, Yamashita Uki
Department of Immunology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Int Immunopharmacol. 2009 Apr;9(4):433-8. doi: 10.1016/j.intimp.2009.01.007. Epub 2009 Feb 2.
1-Bromopropane (1-BP) has been widely used as an alternative to ozone-depleting chlorofluorocarbons in various industries. Although the neurotoxicity of 1-BP has been recently reported, there is little information about the effect of 1-BP on the cells in brain by experimental approach. Here we studied the effect of 1-BP on brain-derived neurotrophic factor (BDNF) expression in astrocytes in vitro. The BDNF mRNA level was remarkably decreased by 1-BP in a human astrocytoma cell line, U251, and in mouse primary astrocytes. The DNA-binding and specific reporter activity of cAMP response element-binding transcription factor (CREB), which is one of the key molecules regulating BDNF expression, were reduced by 1-BP in U251 and/or mouse primary astrocytes. Additionally, protein kinase A (PKA) activity was suppressed by 1-BP in U251. These results suggest that BDNF expression was affected by 1-BP through at least PKA.
1-溴丙烷(1-BP)在各个行业中已被广泛用作消耗臭氧层的氯氟烃的替代品。尽管最近有报道称1-BP具有神经毒性,但通过实验方法了解1-BP对脑内细胞影响的信息却很少。在此,我们研究了1-BP对体外培养的星形胶质细胞中脑源性神经营养因子(BDNF)表达的影响。在人星形细胞瘤细胞系U251和小鼠原代星形胶质细胞中,1-BP可显著降低BDNF mRNA水平。环磷酸腺苷反应元件结合转录因子(CREB)是调节BDNF表达的关键分子之一,在U251和/或小鼠原代星形胶质细胞中,1-BP可降低其DNA结合能力和特异性报告基因活性。此外,在U251中,1-BP可抑制蛋白激酶A(PKA)的活性。这些结果表明,1-BP至少通过PKA影响BDNF的表达。