title: Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Mullen
authors.forename: Youssef H
authors.initials: YH
authors.lastname: Zeidan
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielawski
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Kraveka
authors.forename: Alicja
authors.initials: A
authors.lastname: Bielawska
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.forename: Yi-Te
authors.initials: YT
authors.lastname: Hsu
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D051049:Sphingosine N-Acyltransferase; D015854:Up-Regulation / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D002518:Ceramides; D024101:Mitochondrial Proteins; D013109:Sphingomyelins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D010088:Oxidoreductases; C505722:CERS5 protein, human; D051049:Sphingosine N-Acyltransferase; D013108:Sphingomyelin Phosphodiesterase