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	Junfei Jin, Qi Hou, Thomas D Mullen, Youssef H Zeidan, Jacek Bielawski, Jacqueline M Kraveka, Alicja Bielawska, Lina M Obeid, Yusuf A Hannun, Yi-Te Hsu
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 283 Issue 39 Pg. 26509-17 (Sep 26 2008) ISSN: 0021-9258 [Print] United States
PMID	18676372 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	BAX protein, human Ceramides Mitochondrial Proteins Sphingomyelins bcl-2-Associated X Protein Cytochromes c Oxidoreductases CERS5 protein, human Sphingosine N-Acyltransferase Sphingomyelin Phosphodiesterase
Topics	Apoptosis (physiology) Cell Hypoxia (physiology) Cell Line Ceramides (metabolism) Cytochromes c (metabolism) Cytoplasm (metabolism) Humans Mitochondria (metabolism) Mitochondrial Proteins (metabolism) Oxidoreductases (metabolism) Protein Transport (physiology) Second Messenger Systems (physiology) Sphingomyelin Phosphodiesterase (metabolism) Sphingomyelins (metabolism) Sphingosine N-Acyltransferase Up-Regulation (physiology) bcl-2-Associated X Protein (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!