Journal of Biological Chemistry · 2008 · 83 citations · 60 references
Life SciencesBiochemistryCell BiologyApoptosisCell SignalingCellular MetabolismApoptosis RegulationBcl-2 Family ProteinsCellular Responses To HypoxiaHypoxia AdaptationIntrinsic Apoptotic PathwaySphingolipid MetabolismApoptosis Signaling PathwaysBcl-2 Family DysregulationBcl-2 Protein ExpressionCeramide MetabolismCeramide Salvage PathwayHypoxia-reoxygenation InjuryPro-apoptotic Bax ActivationPro-apoptotic Effectors
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.
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