Journal
JOURNAL OF LIPID RESEARCH
Volume 50, Issue 12, Pages 2389-2397Publisher
ELSEVIER
DOI: 10.1194/jlr.M900119-JLR200
Keywords
AMP-activated protein kinase signaling pathway; sphingolipid; cell death
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Funding
- National Institutes of Health [NS40932, NCRR-C06RR018823]
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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.
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