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

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

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Abstract

Ceramide functions as an important second messenger in apoptosis signaling pathways. In this report, we show that treatment of NT-2 neuronal precursor cells with hypoxia/reoxygenation (H/R) resulted in ceramide up-regulation. This elevation in ceramide was primarily due to the actions of acid sphingomyelinase and ceramide synthase LASS 5, demonstrating the action of the salvage pathway. Hypoxia/reoxygenation treatment led to Bax translocation from the cytoplasm to mitochondria and cytochrome c release from mitochondria. Down-regulation of either acid sphingomyelinase or LASS 5-attenuated ceramide accumulation and H/R-induced Bax translocation to mitochondria. Overall, we have demonstrated that ceramide upregulation following H/R is pertinent to Bax activation to promote cell death.

Original languageEnglish (US)
Pages (from-to)26509-26517
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number39
DOIs
StatePublished - Sep 26 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jin, J., Hou, Q., Mullen, T. D., Zeidan, Y. H., Bielawski, J., Kraveka, J. M., Bielawska, A., Obeid, L. M., Hannun, Y. A., & Hsu, Y. T. (2008). Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced bax redistribution to mitochondria in NT-2 cells. Journal of Biological Chemistry, 283(39), 26509-26517. https://doi.org/10.1074/jbc.M801597200