Repeated Lipopolysaccharide Stimulation Induces Cellular Senescence in BV2 Cells
Repeated Lipopolysaccharide Stimulation Induces Cellular Senescence in BV2 Cells
复制标题
重复脂多糖刺激诱导 BV2 细胞衰老
DOI：
10.1159/000330254
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发表时间：
2012-01
影响因子：
2.4
通讯作者：
Chen, Sheng-Di
中科院分区：
文献类型：
--
作者：
Yu, Hong-Mei;Wang, Xi-Jin;Zhao, Yan-Min;Luo, Xiao-Guang;Feng, Yu;Ren, Yan;Shang, Hong;He, Zhi-Yi;Luo, Xiao-Meng;Chen, Sheng-Di
背景和目的：小胶质细胞在神经退行性疾病中的双重作用一直存在争议。最近的研究表明，小胶质细胞的衰老可能是关键的决定因素。当小胶质细胞老化时，它们的功能异常，无法对刺激做出正确的反应，最终促进神经退行性变。越来越多的证据表明，炎症和衰老之间有着密切的关系。由于神经炎症的特征是小胶质细胞活化，我们评估了小胶质细胞的重复活化是否会导致衰老。方法：每48 h用脂多糖（LPS; 10 ng/ml）重复刺激小胶质细胞系BV 2，并通过β-半乳糖苷酶染色和衰老相关异染色质病灶的存在以及通过流式细胞术检测细胞周期阻滞来评价衰老。Western blot检测衰老相关蛋白p53的表达。结果如下：对照细胞中几乎检测不到β-半乳糖苷酶染色，而随着LPS重复刺激，β-半乳糖苷酶染色倾向于增加，并且在LPS刺激6次后在大多数细胞中呈阳性。同样，衰老相关的异染色质病灶在LPS反复刺激的细胞中最突出，而在对照细胞或接受单次刺激的细胞中几乎检测不到。p53表达在接受LPS刺激6次的细胞中最高，并且在同一组中观察到最大数量的细胞停滞在G 0/G1期。结论：小胶质细胞在反复激活后趋于衰老，这意味着小胶质细胞衰老可能在多次炎症刺激后开始。
Background and Aim: The dual action of microglia in neurodegenerating diseases has been controversial for some time. Recent studies indicate that microglia senescence might be the key determinant. When microglia age, they function abnormally and fail to respond correctly to stimuli, which eventually promotes neurodegeneration. Accumulating evidence has shown a close relationship between inflammation and aging. Since neuroinflammation is characterized by microglia activation, we assessed if the repeated activation of microglia would lead to senescence. Method: The microglia cell line BV2 was repeatedly stimulated every 48 h with lipopolysaccharide (LPS; 10 ng/ml) and senescence was evaluated by β-galactosidase staining and the presence of senescence-associated heterochromatic foci as well as by cell cycle arrest detection by flow cytometry. The senescence-associated protein p53 was also detected by Western blot. Results: β-Galactosidase staining was barely detectable in control cells, while it tended to increase with repeated LPS stimulation and was positive in most cells after stimulation with LPS 6 times. Similarly, senescence-associated heterochromatic foci were most prominent in cells repeatedly stimulated with LPS, while almost undetectable in control cells or cells receiving a single stimulation. p53 expression was highest in the cells that received LPS stimulation 6 times, and the largest number of cells arrested in the G0/G1 phase was observed in this same group. Conclusion: Microglial cells tend to undergo senescence after repeated activation, implying that microglia senescence may start after multiple inflammatory challenges.
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影响因子：
4.2
作者：
Conde, Jessica R.;Streit, Wolfgang J.
通讯作者：
Streit, Wolfgang J.
影响因子：
6.2
作者：
J. Tusell;Aroa Ejarque‐Ortíz;P. Mancera;C. Solà;J. Saura;J. Serratosa
通讯作者：
J. Tusell;Aroa Ejarque‐Ortíz;P. Mancera;C. Solà;J. Saura;J. Serratosa
影响因子：
5.3
作者：
Guillaume Voghel;N. Thorin-Trescases;N. Farhat;Albert Nguyen;L. Villeneuve;Aida M. Mamarbachi;A. Fortier-A.
通讯作者：
Guillaume Voghel;N. Thorin-Trescases;N. Farhat;Albert Nguyen;L. Villeneuve;Aida M. Mamarbachi;A. Fortier-A.
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
6.2
作者：
Streit, WJ;Sammons, NW;Sparks, DL
通讯作者：
Sparks, DL