LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the AMPK activator AICAR.
LPS inhibits caspase 3-dependent apoptosis in RAW264.7 macrophages induced by the AMPK activator AICAR.
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LPS 抑制 AMPK 激活剂 AICAR 诱导的 RAW264 7 巨噬细胞中 caspase 3 依赖性细胞凋亡
DOI：
10.1016/j.bbrc.2014.04.008
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发表时间：
2014
影响因子：
3.1
通讯作者：
Niederberger E.
中科院分区：
文献类型：
--
作者：
Russe OQ;Möser CV;Kynast KL;King TS;Olbrich K;Grösch S;Geisslinger G;Niederberger E.
AMP激活的激酶是一种细胞能量传感器，在ATP消耗增加的阶段被激活。它的激活已经与许多有益的作用相关，例如分别减少炎症过程以及糖尿病和肥胖症的疾病进展。此外，AMPK激活与癌症和血管细胞中细胞周期停滞和细胞凋亡的诱导有关，表明它可能对癌症和动脉粥样硬化的治疗具有治疗作用。然而，AMPK对巨噬细胞增殖的影响，其也在动脉粥样硬化斑块的形成和炎症过程中发挥关键作用，迄今为止尚未受到关注。我们已经评估了AICAR和二甲双胍诱导的AMPK活化对巨噬细胞细胞活力的影响，分别有和没有炎症刺激。在没有炎症刺激的细胞中，我们发现了强烈的caspase 3依赖性凋亡诱导，与mTOR水平降低和p21表达增加相关。有趣的是，这些作用可以被细菌脂多糖（LPS）的共刺激抑制，但不是由其他促炎细胞因子，表明AICAR诱导凋亡通过AMPK在TLR 4-pathway dependent manner.In结论，我们的研究结果表明，AMPK激活不仅与积极的影响，但也可能有助于危险因素，通过干扰巨噬细胞的重要功能。LPS能够恢复AMPK相关凋亡的事实可能表明TLR 4激动剂在防止免疫细胞的不利细胞死亡中的重要作用。
AMP-activated kinase is a cellular energy sensor which is activated in stages of increased ATP consumption. Its activation has been associated with a number of beneficial effects such as decreasing inflammatory processes and the disease progress of diabetes and obesity, respectively. Furthermore, AMPK activation has been linked with induction of cell cycle arrest and apoptosis in cancer and vascular cells, indicating that it might have a therapeutic impact for the treatment of cancer and atherosclerosis. However, the impact of AMPK on the proliferation of macrophages, which also play a key role in the formation of atherosclerotic plaques and in inflammatory processes, has not been focused so far. We have assessed the influence of AICAR- and metformin-induced AMPK activation on cell viability of macrophages with and without inflammatory stimulation, respectively. In cells without inflammatory stimulation, we found a strong induction of caspase 3-dependent apoptosis associated with decreased mTOR levels and increased expression of p21. Interestingly, these effects could be inhibited by co-stimulation with bacterial lipopolysaccharide (LPS) but not by other proinflammatory cytokines suggesting that AICAR induces apoptosis via AMPK in a TLR4-pathway dependent manner.In conclusion, our results revealed that AMPK activation is not only associated with positive effects but might also contribute to risk factors by disturbing important features of macrophages. The fact that LPS is able to restore AMPK-associated apoptosis might indicate an important role of TLR4 agonists in preventing unfavorable cell death of immune cells.
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DOI：
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发表时间：
--
期刊：
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影响因子：
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作者：
T. Sengupta;Gilles M. Leclerc;Ting Ting Hsieh-Kinser-Ting;Guy J Leclerc;I. Singh;J. Barredo;Email Tapas;Gilles;Ting Ting-Ting
通讯作者：
T. Sengupta;Gilles M. Leclerc;Ting Ting Hsieh-Kinser-Ting;Guy J Leclerc;I. Singh;J. Barredo;Email Tapas;Gilles;Ting Ting-Ting
影响因子：
4.4
作者：
Moeser, Christine V.;Kynast, Katharina;Niederberger, Ellen
通讯作者：
Niederberger, Ellen
影响因子：
11.2
作者：
Liang J;Mills GB
通讯作者：
Mills GB
影响因子：
4.1
作者：
López, JM;Santidrián, AF;Gil, J
通讯作者：
Gil, J
DOI：
10.1152/ajprenal.00034.2011
发表时间：
2011-12-01
影响因子：
4.2
作者：
Lieberthal, Wilfred;Zhang, Leiqing;Levine, Jerrold S.
通讯作者：
Levine, Jerrold S.