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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Selective regulation of growth factor expression in cultured cortical astrocytes by neuro-pathological toxins.
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Selective regulation of growth factor expression in cultured cortical astrocytes by neuro-pathological toxins.

机译：神经病理毒素对培养的皮质星形胶质细胞中生长因子表达的选择性调节。

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摘要

Astrocytes are integrated in the complex regulation of neurodegeneration and neuronal damage in the CNS. It is well-known that astroglia produces a plethora of growth factors which might be protective for neurons. Growth factors prevent neurons from cell death and promote proliferation and differentiation of precursor cells. Previous data suggest that astrocytes may respond to toxic stimuli by a selective mobilization of guarding molecules. In the present study, we have investigated the potency of different pathological stimuli such as lipopolysaccharides, tumor necrosis factor alpha, glutamate, and hydrogen peroxide to activate cultured cortical astroglia and stimulate growth factor expression. Astroglial cultures were exposed to the above factors for 24h at non-toxic concentrations for astrocytes. Growth factor expression was analyzed by real-time PCR, oligo-microarray technique, and ELISA. Insulin-like growth factor-1 was selectively down-regulated by lipopolysaccharides and tumor necrosis factor alpha, bone morphogenetic protein 6 by all stimuli. In contrast, lipopolysaccharides, tumor necrosis factor alpha, and glutamate increased leukemia inhibitory factor. Fibroblast growth factor 2 was up-regulated by lipopolysaccharides and tumor necrosis factor alpha and down-regulated by hydrogen peroxide. Besides hydrogen peroxide, all other stimuli promoted vascular epithelial growth factor A mRNA and protein expression. It appears that lipopolysaccharides but not tumor necrosis factor alpha effects on vascular epithelial growth factor A depend on the classic NFkappaB pathway. Our data clearly demonstrate that astroglia actively responses to diverse pathological compounds by a selective expression pattern of growth factors. These findings make astrocytes likely candidates to participate in disease-specific characteristics of neuronal support or damage.
机译：星形胶质细胞整合在中枢神经系统的神经变性和神经元损伤的复杂调控中。众所周知，星形胶质细胞会产生过多的生长因子，可能对神经元具有保护作用。生长因子可防止神经元细胞死亡，并促进前体细胞的增殖和分化。先前的数据表明，星形胶质细胞可能通过选择性动员保护分子来响应毒性刺激。在本研究中，我们研究了不同病理刺激（例如脂多糖，肿瘤坏死因子α，谷氨酸和过氧化氢）激活培养的皮质星形胶质细胞和刺激生长因子表达的效力。星形胶质细胞培养物在星形胶质细胞无毒浓度下暴露于上述因素24小时。生长因子表达通过实时PCR，寡芯片技术和ELISA进行分析。脂多糖和肿瘤坏死因子α，骨形态发生蛋白6被所有刺激选择性地下调胰岛素样生长因子-1。相反，脂多糖，肿瘤坏死因子α和谷氨酸可增加白血病抑制因子。成纤维细胞生长因子2被脂多糖和肿瘤坏死因子α上调，而过氧化氢被下调。除过氧化氢外，所有其他刺激均促进血管上皮生长因子A mRNA和蛋白质表达。似乎脂多糖而不是肿瘤坏死因子α对血管上皮生长因子A的作用取决于经典的NFκB途径。我们的数据清楚地表明，星形胶质细胞通过生长因子的选择性表达模式对多种病理化合物做出积极反应。这些发现使星形胶质细胞有可能参与神经元支持或损伤的疾病特异性特征。

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