Department of Neurosurgery, Affiliated Dongtai Hospital of Nantong University, Medical College, Nantong University, Yancheng, 224200 Jiangsu, People's Republic of China.
Cell Mol Neurobiol. 2011 Oct;31(7):1047-56. doi: 10.1007/s10571-011-9704-3. Epub 2011 May 14.
Src-suppressed C kinase substrate (SSeCKS), a protein kinase C substrate, is a major lipopolysaccharide (LPS) response protein. In addition, β-1,4 Galactosyltransferase-I (β-1,4-GalT-I) also plays an important role in the inflammation reactions of nervous system. It was reported that both SSeCKS and β-1,4-GalT-I were involved in the LPS-induced tumor necrosis factor-alpha (TNF-α) expression in rat primary astrocytes. However, the functional interaction between SSeCKS and β-1,4-GalT-I in the LPS-induced TNF-α secretion remains unclear. Therefore, in this study, using the inflammation model of astrocytes treated by LPS in vitro, we found that the changed expressions of SSeCKS and β-1,4-GalT-I participated in LPS-induced TNF-α secretion through p38, JNK, and ERK signal transduction pathways in rat primary astrocytes. Knockdown by small-interfering RNAs (siRNAs) or overexpression of SSeCKS and β-1,4-GalT-I could influence Mitogen-activated protein kinases (MAPKs) signaling pathways activation and TNF-α secretion. Besides, we confirmed that knockdown of SSeCKS could prevent the induction of β-1,4-GalT-I in this process. Inversely, β-1,4-GalT-I had no significant effect on SSeCKS expression in the same way. In summary, our data indicated that SSeCKS could regulate LPS-induced TNF-α secretion through β-1,4-GalT-I in rat primary astrocytes.
Src 抑制型 C 激酶底物(SSeCKS)是蛋白激酶 C 的底物,是主要的脂多糖(LPS)反应蛋白。此外,β-1,4 半乳糖基转移酶-I(β-1,4-GalT-I)在神经系统炎症反应中也起着重要作用。有报道称,SSeCKS 和β-1,4-GalT-I 都参与了 LPS 诱导的大鼠原代星形胶质细胞中肿瘤坏死因子-α(TNF-α)的表达。然而,SSeCKS 和β-1,4-GalT-I 在 LPS 诱导的 TNF-α分泌中的功能相互作用尚不清楚。因此,在本研究中,我们通过体外 LPS 处理星形胶质细胞的炎症模型发现,SSeCKS 和β-1,4-GalT-I 的表达变化通过 p38、JNK 和 ERK 信号转导通路参与了 LPS 诱导的大鼠原代星形胶质细胞中 TNF-α的分泌。通过小干扰 RNA(siRNA)敲低或 SSeCKS 和β-1,4-GalT-I 的过表达可以影响丝裂原激活蛋白激酶(MAPKs)信号通路的激活和 TNF-α的分泌。此外,我们还证实,在此过程中敲低 SSeCKS 可以阻止β-1,4-GalT-I 的诱导。相反,β-1,4-GalT-I 对 SSeCKS 表达没有显著影响。综上所述,我们的数据表明,SSeCKS 可以通过β-1,4-GalT-I 调节 LPS 诱导的 TNF-α 在大鼠原代星形胶质细胞中的分泌。