Literature DB >> 19528633

AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells.

Junfei Jin1, Thomas D Mullen, Qi Hou, Jacek Bielawski, Alicja Bielawska, Xiaoming Zhang, Lina M Obeid, Yusuf A Hannun, Yi-Te Hsu.   

Abstract

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.

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Year:  2009        PMID: 19528633      PMCID: PMC2781311          DOI: 10.1194/jlr.M900119-JLR200

Source DB:  PubMed          Journal:  J Lipid Res        ISSN: 0022-2275            Impact factor:   5.922


  45 in total

1.  Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells.

Authors:  M Egawa; H Kamata; A Kushiyama; H Sakoda; M Fujishiro; N Horike; M Yoneda; Y Nakatsu; Guo Ying; Zhang Jun; Y Tsuchiya; K Takata; H Kurihara; T Asano
Journal:  Placenta       Date:  2008-10-23       Impact factor: 3.481

2.  Nonionic detergents induce dimerization among members of the Bcl-2 family.

Authors:  Y T Hsu; R J Youle
Journal:  J Biol Chem       Date:  1997-05-23       Impact factor: 5.157

3.  Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity.

Authors:  Stefka Spassieva; Jae-Gu Seo; James C Jiang; Jacek Bielawski; Fernando Alvarez-Vasquez; S Michal Jazwinski; Yusuf A Hannun; Lina M Obeid
Journal:  J Biol Chem       Date:  2006-09-01       Impact factor: 5.157

4.  Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.

Authors:  Junfei Jin; Qi Hou; Thomas D Mullen; Youssef H Zeidan; Jacek Bielawski; Jacqueline M Kraveka; Alicja Bielawska; Lina M Obeid; Yusuf A Hannun; Yi-Te Hsu
Journal:  J Biol Chem       Date:  2008-08-01       Impact factor: 5.157

Review 5.  Radiation and ceramide-induced apoptosis.

Authors:  Richard Kolesnick; Zvi Fuks
Journal:  Oncogene       Date:  2003-09-01       Impact factor: 9.867

6.  AMPK activator, AICAR, inhibits palmitate-induced apoptosis in osteoblast.

Authors:  Ji-Eun Kim; Myun-Whan Ahn; Suk-Hwan Baek; In Kyu Lee; Yong-Woon Kim; Jong-Yeon Kim; Jin-Myoung Dan; So-Young Park
Journal:  Bone       Date:  2008-04-10       Impact factor: 4.398

7.  Retinoic acid leads to cytoskeletal rearrangement through AMPK-Rac1 and stimulates glucose uptake through AMPK-p38 MAPK in skeletal muscle cells.

Authors:  Yun Mi Lee; Jung Ok Lee; Jin-Hee Jung; Ji Hae Kim; Sun-Hwa Park; Ji Man Park; Eung-Kyun Kim; Pann-Ghill Suh; Hyeon Soo Kim
Journal:  J Biol Chem       Date:  2008-10-16       Impact factor: 5.157

8.  Follicle-stimulating hormone inhibits adenosine 5'-monophosphate-activated protein kinase activation and promotes cell proliferation of primary granulosa cells in culture through an Akt-dependent pathway.

Authors:  Pradeep P Kayampilly; K M J Menon
Journal:  Endocrinology       Date:  2008-10-16       Impact factor: 4.736

9.  Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death.

Authors:  Yusuke Nakatsu; Yaichiro Kotake; Atsuko Hino; Shigeru Ohta
Journal:  Toxicol Appl Pharmacol       Date:  2008-04-09       Impact factor: 4.219

10.  Cloning of human acetyl-CoA carboxylase cDNA.

Authors:  J Ha; S Daniel; I S Kong; C K Park; H J Tae; K H Kim
Journal:  Eur J Biochem       Date:  1994-01-15
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  37 in total

1.  Compound C stimulates heme oxygenase-1 gene expression via the Nrf2-ARE pathway to preserve human endothelial cell survival.

Authors:  Xiao-Ming Liu; Kelly J Peyton; Ahmad R Shebib; Hong Wang; William Durante
Journal:  Biochem Pharmacol       Date:  2011-05-24       Impact factor: 5.858

2.  Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death.

Authors:  María José Hernández-Corbacho; Daniel Canals; Mohamad M Adada; Mengling Liu; Can E Senkal; Jae Kyo Yi; Cungui Mao; Chiara Luberto; Yusuf A Hannun; Lina M Obeid
Journal:  J Biol Chem       Date:  2015-08-28       Impact factor: 5.157

3.  Inhibition of AMP-activated protein kinase pathway sensitizes human leukemia K562 cells to nontoxic concentration of doxorubicin.

Authors:  Qun Zhu; Bo Shen; Boshao Zhang; Wei Zhang; Steve H Chin; Junfei Jin; Duan-fang Liao
Journal:  Mol Cell Biochem       Date:  2010-03-26       Impact factor: 3.396

4.  Compound C inhibits vascular smooth muscle cell proliferation and migration in an AMP-activated protein kinase-independent fashion.

Authors:  Kelly J Peyton; Yajie Yu; Benjamin Yates; Ahmad R Shebib; Xiao-ming Liu; Hong Wang; William Durante
Journal:  J Pharmacol Exp Ther       Date:  2011-05-12       Impact factor: 4.030

5.  The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent.

Authors:  Xiaona Liu; Rishi Raj Chhipa; Ichiro Nakano; Biplab Dasgupta
Journal:  Mol Cancer Ther       Date:  2014-01-13       Impact factor: 6.261

Review 6.  Ceramide synthases at the centre of sphingolipid metabolism and biology.

Authors:  Thomas D Mullen; Yusuf A Hannun; Lina M Obeid
Journal:  Biochem J       Date:  2012-02-01       Impact factor: 3.857

7.  Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74.

Authors:  Daniel Heinrichs; Meike Knauel; Christian Offermanns; Marie-Luise Berres; Andreas Nellen; Lin Leng; Petra Schmitz; Richard Bucala; Christian Trautwein; Christian Weber; Jürgen Bernhagen; Hermann E Wasmuth
Journal:  Proc Natl Acad Sci U S A       Date:  2011-10-03       Impact factor: 11.205

8.  Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis.

Authors:  Fanli Meng; Xiaotian Su; Wei Li; Yinan Zheng
Journal:  Exp Ther Med       Date:  2017-03-29       Impact factor: 2.447

9.  Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo.

Authors:  Quanlu Duan; Ping Song; Ye Ding; Ming-Hui Zou
Journal:  Br J Pharmacol       Date:  2017-05-31       Impact factor: 8.739

10.  AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction.

Authors:  Katarzyna A Cieslik; George E Taffet; Jeffrey R Crawford; JoAnn Trial; Patricia Mejia Osuna; Mark L Entman
Journal:  J Mol Cell Cardiol       Date:  2013-07-19       Impact factor: 5.000

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