Upregulation of p21Cip1 in activated glial cells
Upregulation of p21Cip1 in activated glial cells
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DOI：
10.1002/glia.20781
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发表时间：
2009-04
期刊：
影响因子：
6.2
通讯作者：
J. Tusell;Aroa Ejarque‐Ortíz;P. Mancera;C. Solà;J. Saura;J. Serratosa
中科院分区：
文献类型：
--
作者：
J. Tusell;Aroa Ejarque‐Ortíz;P. Mancera;C. Solà;J. Saura;J. Serratosa
cdk抑制剂p21 Cip 1，也称为p21 Cip 1/Waf 1，在几种细胞类型中密切参与生长停滞与细胞分化的偶联。p21 Cip 1是一种多功能蛋白，可能在不同水平上调节细胞周期进程。在最近的一项研究中，我们发现野生型和p21 Cip 1 −/−小鼠的神经胶质细胞之间的增殖速率没有差异。在本研究中，我们使用混合胶质细胞培养物、小胶质细胞富集培养物和星形胶质细胞富集培养物，研究了野生型和p21 Cip 1 −/−小鼠胶质细胞之间的胶质细胞活化差异。我们比较了脂多糖和两种形式（寡聚体和纤维状）的1 - 42 β-淀粉样肽对胶质细胞活化的影响。与野生型小鼠的神经胶质细胞相比，我们观察到p21 Cip 1 −/−神经胶质细胞中核因子κ B的核转位减弱。相比之下，p21 Cip 1 −/−小胶质细胞中肿瘤坏死因子-α的释放增强。此外，脂多糖诱导的胶质细胞活化和1 - 42 β-淀粉样肽的纤维形式上调p21 Cip 1。我们的研究结果支持p21 Cip 1在神经胶质细胞，特别是小胶质细胞的激活中的作用。© 2008 Wiley利斯公司
The cdk inhibitor p21Cip1, also named p21Cip1/Waf1, is intimately involved in coupling growth arrest to cellular differentiation in several cell types. p21Cip1 is a multifunctional protein that might regulate cell‐cycle progression at different levels. In a recent study, we found no differences in the rate of proliferation between glial cells from wild‐type and p21Cip1−/− mice. In the present study, we examined differences in glial activation between glial cells from wild‐type and p21Cip1−/− mice, using mixed glial cultures, microglia‐enriched cultures, and astrocyte‐enriched cultures. We compared the effect of lipopolysaccharide and two forms (oligomeric and fibrillar) of the 1‐42 β‐amyloid peptide on glial activation. We observed an attenuation of nuclear translocation of the nuclear factor kappa‐B in p21Cip1−/− glial cells, when compared with glial cells from wild‐type mice. In contrast, tumor necrosis factor‐α release was enhanced in p21Cip1−/−microglial cells. In addition glial activation induced by lipopolysaccharide and the fibrillar form of the 1‐42 β‐amyloid peptide upregulated p21Cip1. Our results support a role for p21Cip1 in the activation of glial cells, particularly in microglia. © 2008 Wiley‐Liss, Inc.