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P53 mediates ceramide-induced apoptosis in SKN-SH cells

Oncogene volume 21, pages 2020–2028 (2002)Cite this article

Abstract

Ceramide induces apoptotic cell death in a dose- and time-dependent manner in neuroblastoma SKN-SH cells. Pretreatment with caspase inhibitors blocks cell death, suggesting that a set of caspase activities including caspase 1, as well as caspase 3, are involved in ceramide-induced apoptosis in SKN-SH cells. Treatment with a caspase inhibitor 3 h after ceramide addition did not inhibit cell death, although caspase activity was substantially reduced. Ceramide-induced apoptosis is accompanied by accumulation of p53 followed by an increase of Bax and decrease of Bcl-2 levels. Inhibition of p53 expression with p53 antisense oligonucleotides inhibits apoptosis and prevents the increase in Bax and decrease in Bcl-2. Furthermore, pretreatment with p53 antisense oligonucleotides markedly inhibits the induction of caspase activity. These results suggest that p53 regulates the ratio Bcl-2/Bax and the expression/activation of caspases during ceramide-induced apoptosis in SKN-SH cells. Caspase inhibition did not alter the expression of p53, Bcl-2 and Bax. Thus ceramide-induced reduction in the Bcl-2/Bax ratio, increase in caspase activity, and apoptosis is dependent upon increases in cellular p53 levels which play a critical role in the regulation of apoptotic cell death.

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Acknowledgements

This research was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ8-PG1-01CN2-0003), Korea Science and Engineering Foundation Grant (2000-2-21300-004-3), Korea Research Foundation Grant (KRF-2000-015-FP0045), and National Creative Research Initiative Program from MOST (2000-2003). JV Bonventre was supported by grants from the National Institutes of Health DK 39773, DK 38452 and NS 10828.

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Authors and Affiliations

  1. Department of Anatomy, College of Medicine, BioGrand Inc., MRC, Chung-Ang University, Seoul, 156-756, Korea

    Sung Su Kim, Hee-Sun Chae, Jae-Hyung Bach, Myoung Woo Lee, Kyung Yong Kim, Won Bok Lee & Young-Min Jung

  2. Biomedical Brain Research Center, NIH, 122-701, Korea

    Yoo-Hun Suh

  3. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Sung Su Kim & Joseph V Bonventre

  4. Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer's Dementia, Neuroscience Research Institute, MRC, Seoul National University, Seoul, 110-799, Korea

    Yoo-Hun Suh

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Correspondence to Joseph V Bonventre.

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Kim, S., Chae, HS., Bach, JH. et al. P53 mediates ceramide-induced apoptosis in SKN-SH cells. Oncogene 21, 2020–2028 (2002). https://doi.org/10.1038/sj.onc.1205037

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