AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
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DOI：
10.1194/jlr.m900119-jlr200
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发表时间：
2009-12-01
影响因子：
6.5
通讯作者：
Hsu, Yi-Te
中科院分区：
文献类型：
--
作者：
Jin, Junfei;Mullen, Thomas D.;Hsu, Yi-Te
化合物C通常被用作amp活化蛋白激酶（AMPK）的抑制剂，AMPK是细胞中关键的能量传感器。在本研究中，我们发现化合物C处理MCF7细胞导致Bax从细胞质重新分布到线粒体和细胞死亡。然而，这种影响与AMPK无关。此外，我们发现用这种化合物处理导致神经酰胺的生产增强。定量PCR和神经酰胺合成酶活性分析表明，神经酰胺合成酶5 （LASS/CerS 5）参与了化合物c诱导的神经酰胺上调。研究发现，下调LASS/CerS 5可减弱化合物c介导的神经酰胺产生、Bax再分布和细胞死亡。-Jin， J.， T. D. Mullen， Q. Hou， J. Bielawski， A. Bielawska， X. Zhang， L. M. Obeid， Y. A. Hannun, Y-T。许。AMPK抑制剂化合物C刺激神经酰胺的产生，促进MCF7乳腺癌细胞Bax的再分配和凋亡。[j] .油脂杂志。2009。: 2389 - 2397。
Compound C is commonly used as an inhibitor of AMP-activated protein kinase (AMPK), which serves as a key energy sensor in cells. In this study, we found that Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death. However, this effect does not involve AMPK. In addition, we found that treatment with this compound leads to an enhanced ceramide production. Analyses by quantitative PCR and ceramide synthase activity assay suggest that ceramide synthase 5 (LASS/CerS 5) is involved in Compound C-induced ceramide upregulation. Downregulation of LASS/CerS 5 was found to attenuate Compound C-mediated ceramide production, Bax redistribution, and cell death.-Jin, J., T. D. Mullen, Q. Hou, J. Bielawski, A. Bielawska, X. Zhang, L. M. Obeid, Y. A. Hannun, and Y-T. Hsu. AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells. J. Lipid Res. 2009. 50: 2389-2397.