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Mitochondrially targeted ceramides preferentially promote autophagy, retard cell growth,and induce apoptosis

Hou Q, Jin J, Zhou H, Novgorodov SA, Bielawska A, Szulc ZM, Hannun YA, Obeid LM, Hsu YT.

Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P R China.

 

Abstract:

C6-pyridinium ceramide (C6-Pyr-Cer)-induced Bax translocation to mitochondria is partially inhibited by zVAD-fmk. A: GFP-Bax-stable MCF7 cells were treated with 10 ng/ml TNF-α (16 h), 0.2 μM staurosporine (6 h), or 20 μM C6-pyridinium ceramide (16 h) either in the absence or presence of 50 μM zVAD-fmk. Cells were visualized by fluorescence microscopy. B: A quantitative analysis of the effect of zVAD-fmk on regulation of TNF-α, staurosporine (STS), and C6-pyridinium ceramide-mediated Bax translocation to mitochondria. Percentages of cells having GFP-Bax localized to mitochondria were averaged from three separate visual fields. The study was carried out three times. C: MCF7 cells stably expressing GFP-Bax were treated with the above-stated compounds. Treated cells were then separated into soluble protein (C) and heavy membrane (M) fractions. Protein samples were analyzed by Western blotting with an anti-Bax antibody. 

 

Journal of Lipid Research,2011,52:278-288.

 

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