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 up-regulation following H/R is pertinent to Bax activation to promote cell death.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology*
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Cell Hypoxia / physiology
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Cell Line
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Ceramides / metabolism*
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Cytochromes c / metabolism
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Cytoplasm / metabolism
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Humans
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Mitochondria / metabolism*
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Mitochondrial Proteins / metabolism*
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Oxidoreductases / metabolism
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Protein Transport / physiology
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Second Messenger Systems / physiology*
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Sphingomyelin Phosphodiesterase / metabolism
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Sphingomyelins / metabolism*
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Sphingosine N-Acyltransferase
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Up-Regulation / physiology
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bcl-2-Associated X Protein / metabolism*
Substances
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BAX protein, human
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Ceramides
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Mitochondrial Proteins
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Sphingomyelins
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bcl-2-Associated X Protein
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Cytochromes c
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Oxidoreductases
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CERS5 protein, human
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Sphingosine N-Acyltransferase
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Sphingomyelin Phosphodiesterase