PMID- 14523050
OWN - NLM
STAT- MEDLINE
DCOM- 20040903
LR  - 20210217
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 45
IP  - 1
DP  - 2004 Jan
TI  - Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase 
      in macrophages.
PG  - 99-105
AB  - It was reported previously that ceramide-1-phosphate (Cer-1-P) is mitogenic for 
      fibroblasts (Gomez-Munoz, A., P. A. Duffy, A. Martin, L. O'Brien, H-S. Byun, R. 
      Bittman, and D. N. Brindley. 1995. Mol. Pharmacol. 47: 883-889; Gomez-Munoz, A., 
      L. M. Frago, L. Alvarez, and I. Varela-Nieto. 1997. Biochem. J. 325: 435-440). We 
      now show that Cer-1-P prevents cell death in bone-marrow-derived macrophages 
      (BMDMs) after withdrawal of macrophage colony-stimulating factor (M-CSF). Removal 
      of M-CSF is known to induce apoptosis in these cells. Cer-1-P blocked activation 
      of the caspase-9/caspase-3 pathway and prevented DNA fragmentation, indicating 
      that the enhancement of cell survival was due to inhibition of apoptosis. M-CSF 
      deprivation resulted in activation of acid sphingomyelinase (A-SMase), increased 
      ceramide levels, and a decrease in intracellular Cer-1-P. Exogenously added 
      Cer-1-P inhibited A-SMase in intact BMDMs at concentrations that also prevented 
      apoptosis. Cer-1-P also inhibited A-SMase in cell homogenates, suggesting a 
      possible direct physical interaction of Cer-1-P with the enzyme. In conclusion, 
      these data demonstrate that Cer-1-P blocks apoptosis in BMDMs through inhibition 
      of A-SMase, thereby reducing ceramide generation. This adds a new dimension to 
      the understanding of the metabolic interrelationship of ceramides and Cer-1-P, 
      and shows how altering the balance of intracellular levels of these mediators can 
      affect cell survival.
FAU - Gomez-Munoz, Antonio
AU  - Gomez-Munoz A
AD  - Department of Biochemistry and Molecular Biology, University of the Basque 
      Country, PO Box 644, 48080 Bilbao, Spain. gbpgomua@lg.ehu.es
FAU - Kong, Jennifer Y
AU  - Kong JY
FAU - Salh, Bill
AU  - Salh B
FAU - Steinbrecher, Urs P
AU  - Steinbrecher UP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031001
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Ceramides)
RN  - 0 (ceramide 1-phosphate)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp9 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Caspase 3
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Cells, Cultured
MH  - Ceramides/*pharmacology
MH  - Enzyme Activation
MH  - Female
MH  - Macrophages/*cytology/drug effects/*enzymology
MH  - Mice
MH  - Sphingomyelin Phosphodiesterase/*antagonists & inhibitors/*metabolism
EDAT- 2003/10/03 05:00
MHDA- 2004/09/04 05:00
CRDT- 2003/10/03 05:00
PHST- 2003/10/03 05:00 [pubmed]
PHST- 2004/09/04 05:00 [medline]
PHST- 2003/10/03 05:00 [entrez]
AID - S0022-2275(20)31925-8 [pii]
AID - 10.1194/jlr.M300158-JLR200 [doi]
PST - ppublish
SO  - J Lipid Res. 2004 Jan;45(1):99-105. doi: 10.1194/jlr.M300158-JLR200. Epub 2003 
      Oct 1.