Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.
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.
Jin
Junfei
J
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Hou
Qi
Q
Mullen
Thomas D
TD
Zeidan
Youssef H
YH
Bielawski
Jacek
J
Kraveka
Jacqueline M
JM
Bielawska
Alicja
A
Obeid
Lina M
LM
Hannun
Yusuf A
YA
Hsu
Yi-Te
YT
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*
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