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 Zeidan, Jacek Bielawski, Jacqueline M. Kraveka, Alicja Bielawska, Lina M. Obeid, Yusuf A. Hannun, Yi Te Hsu

Research output: Contribution to journalArticle

54 Citations (Scopus)

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
Externally publishedYes

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Salvaging
Mitochondria
Sphingomyelins
Ceramides
Hydrolysis
Sphingomyelin Phosphodiesterase
Up-Regulation
Cell Hypoxia
Acids
Second Messenger Systems
Cell death
Cytochromes c
Cytoplasm
Cell Death
Down-Regulation
Chemical activation
methyl(arginyl)-lysyl-prolyl-tryptophyl-tert-leucyl-leucine
Hypoxia
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced bax redistribution to mitochondria in NT-2 cells. / Jin, Junfei; Hou, Qi; Mullen, Thomas D.; Zeidan, Youssef; Bielawski, Jacek; Kraveka, Jacqueline M.; Bielawska, Alicja; Obeid, Lina M.; Hannun, Yusuf A.; Hsu, Yi Te.

In: Journal of Biological Chemistry, Vol. 283, No. 39, 26.09.2008, p. 26509-26517.

Research output: Contribution to journalArticle

Jin, J, Hou, Q, Mullen, TD, Zeidan, Y, Bielawski, J, Kraveka, JM, Bielawska, A, Obeid, LM, Hannun, YA & Hsu, YT 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, vol. 283, no. 39, pp. 26509-26517. https://doi.org/10.1074/jbc.M801597200
Jin, Junfei ; Hou, Qi ; Mullen, Thomas D. ; Zeidan, Youssef ; Bielawski, Jacek ; Kraveka, Jacqueline M. ; Bielawska, Alicja ; Obeid, Lina M. ; Hannun, Yusuf A. ; Hsu, Yi Te. / Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced bax redistribution to mitochondria in NT-2 cells. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 39. pp. 26509-26517.
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