| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print February 10, 2003
Pathology and Laboratory Medicine, University Hospital Groningen, Groningen 9713 GZ
Corresponding Author: b.j.kroesen{at}med.rug.nl
In the present study we describe an ordered formation of long- and very long-chain ceramide species in relation to the progression of BcR triggering induced apoptosis. An early and caspase-independent increase in long-chain ceramide species, in which C16-ceramide predominated, was observed 6 hrs after BcR triggering, prior to the onset of apoptosis. In contrast, very long-chain ceramide species were generated later, at 12 to 24 hrs after BcR triggering. Formation of these very long-chain ceramide species, in which C24-ceramide predominated, required activation of effector caspases. Further studies were conducted to define specific mechanisms of action of the early phase of ceramide generation. BcR triggering resulted in proteasomal activation and degradation of XIAP and subsequent activation of effector caspases. This BcR induced activation of the proteasome was blocked with ISP-1/myriocin, a potent and selective inhibitor of serine palmitoyl transferase which catalyzes the first and rate-limiting step in the de novo formation of ceramide. Both ISP-1 and clasto-lactacystin b-lactone, an irreversible inhibitor of the proteasome, prevented BcR crosslinking-induced XIAP degradation. Importantly, a mutant XIAP, lacking the ubiquitin ligating ring finger motif, was completely resistant to proteasome-mediated degradation, and Ramos-cells over-expressing XIAP became highly resistant to BcR crosslinking induced activation of caspases. Formation of C16-ceramide in response to BcR crosslinking was found unaltered in XIAP over-expressing Ramos cells, whereas C24-ceramide formation was completely abolished. These results demonstrate a novel function for de novo generated long-chain ceramide species, and they provide strong evidence distinguishing at least two major metabolic pathways of ceramide with long-chain ceramides acting upstream of key events in apoptosis whereas very long-chain ceramides are generated downstream of these events. As such, these results provide novel and important insights into the significance of specific ceramide species in defined stages of apoptosis.
J. Biol. Chem, 10.1074/jbc.M210756200
Submitted on October 21, 2002
Revised on February 6, 2003
Accepted on February 10, 2003
BcR-induced apoptosis involves differential regulation of C16- and C24-ceramide formation and sphingolipid dependent activation of the proteasome
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  T. R. Medler, D. N. Petrusca, P. J. Lee, W. C. Hubbard, E. V. Berdyshev, J. Skirball, K. Kamocki, E. Schuchman, R. M. Tuder, and I. Petrache Apoptotic Sphingolipid Signaling by Ceramides in Lung Endothelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 639 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Oda, T. Matsuno, R. Shiihara, S. Ochi, R. Yamauchi, Y. Saito, H. Imagawa, M. Nagahama, M. Nishizawa, and J. Sakurai The relationship between the metabolism of sphingomyelin species and the hemolysis of sheep erythrocytes induced by Clostridium perfringens {alpha}-toxin J. Lipid Res., May 1, 2008; 49(5): 1039 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Stel, B. ten Cate, S. Jacobs, J. W. Kok, D. C. J. Spierings, M. Dondorff, W. Helfrich, H. C. Kluin-Nelemans, L. F. M. H. de Leij, S. Withoff, et al. Fas Receptor Clustering and Involvement of the Death Receptor Pathway in Rituximab-Mediated Apoptosis with Concomitant Sensitization of Lymphoma B Cells to Fas-Induced Apoptosis J. Immunol., February 15, 2007; 178(4): 2287 - 2295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pewzner-Jung, S. Ben-Dor, and A. H. Futerman When Do Lasses (Longevity Assurance Genes) Become CerS (Ceramide Synthases)?: INSIGHTS INTO THE REGULATION OF CERAMIDE SYNTHESIS J. Biol. Chem., September 1, 2006; 281(35): 25001 - 25005. [Full Text] [PDF]
|
|
|
|
|
|
Y. Masukawa, H. Tsujimura, and H. Narita Liquid chromatography-mass spectrometry for comprehensive profiling of ceramide molecules in human hair J. Lipid Res., July 1, 2006; 47(7): 1559 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. J. Hinrichs, K. Klappe, M. van Riezen, and J. W. Kok Drug resistance-associated changes in sphingolipids and ABC transporters occur in different regions of membrane domains J. Lipid Res., November 1, 2005; 46(11): 2367 - 2376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Erdreich-Epstein, L. B. Tran, O. T. Cox, E. Y. Huang, W. E. Laug, H. Shimada, and M. Millard Endothelial apoptosis induced by inhibition of integrins {alpha}v{beta}3 and {alpha}v{beta}5 involves ceramide metabolic pathways Blood, June 1, 2005; 105(11): 4353 - 4361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Becker, K. Kitatani, J. Idkowiak-Baldys, J. Bielawski, and Y. A. Hannun Selective Inhibition of Juxtanuclear Translocation of Protein Kinase C {beta}II by a Negative Feedback Mechanism Involving Ceramide Formed from the Salvage Pathway J. Biol. Chem., January 28, 2005; 280(4): 2606 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I-N. Park, I. J. Cho, and S. G. Kim CERAMIDE, AN APOPTOTIC RHEOSTAT, INHIBITS CCAAT/ENHANCER BINDING PROTEIN-{beta} AND NF-E2-RELATED FACTOR-2 ACTIVATION: THE ROLE IN GLUTATHIONE S-TRANSFERASE A2 GENE REPRESSION Drug Metab. Dispos., September 1, 2004; 32(9): 893 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Marchesini, W. Osta, J. Bielawski, C. Luberto, L. M. Obeid, and Y. A. Hannun Role for Mammalian Neutral Sphingomyelinase 2 in Confluence-induced Growth Arrest of MCF7 Cells J. Biol. Chem., June 11, 2004; 279(24): 25101 - 25111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Saba and T. Hla Point-Counterpoint of Sphingosine 1-Phosphate Metabolism Circ. Res., April 2, 2004; 94(6): 724 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Reiss, B. Oskouian, J. Zhou, V. Gupta, P. Sooriyakumaran, S. Kelly, E. Wang, A. H. Merrill Jr., and J. D. Saba Sphingosine-phosphate Lyase Enhances Stress-induced Ceramide Generation and Apoptosis J. Biol. Chem., January 9, 2004; 279(2): 1281 - 1290. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
