PMID- 30154232
OWN - NLM
STAT- MEDLINE
DCOM- 20190902
LR  - 20210217
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 59
IP  - 11
DP  - 2018 Nov
TI  - Functions of neutral ceramidase in the Golgi apparatus.
PG  - 2116-2125
LID - 10.1194/jlr.M088187 [doi]
AB  - Ceramidases hydrolyze ceramides into sphingosine and fatty acids, with 
      sphingosine being further metabolized into sphingosine-1-phosphate (S1P); thus, 
      ceramidases control the levels of these bioactive sphingolipids in cells and 
      tissues. Neutral ceramidase (nCDase) is highly expressed in colorectal tissues, 
      and a recent report showed that nCDase activity is involved in Wnt/beta-catenin 
      signaling. In addition, the inhibition of nCDase decreases the development and 
      progression of colorectal tumor growth. Here, to determine the action of nCDase 
      in colorectal cancer cells, we focused on the subcellular localization and 
      metabolic functions of this enzyme in HCT116 cells. nCDase was found to be 
      located in both the plasma membrane and in the Golgi apparatus, but it had 
      minimal effects on basal levels of ceramide, sphingosine, or S1P. Cells 
      overexpressing nCDase were protected from the cell death and Golgi fragmentation 
      induced by C6-ceramide, and they showed reduced levels of C6-ceramide and higher 
      levels of S1P and sphingosine. Furthermore, compartment-specific metabolic 
      functions of the enzyme were probed using C6-ceramide and Golgi-targeted 
      bacterial SMase (bSMase) and bacterial ceramidase (bCDase). The results showed 
      that Golgi-specific bCDase also demonstrated resistance against the cell death 
      stimulated by C6-ceramide, and it catalyzed the metabolism of ceramides and 
      produced sphingosine in the Golgi. Targeting bSMase to the Golgi resulted in 
      increased levels of ceramide that were attenuated by the expression of nCDase, 
      also supporting its ability to metabolize Golgi-generated ceramide. These results 
      are critical in understanding the functions of nCDase actions in colorectal 
      cancer cells as well as the compartmentalized pathways of sphingolipid 
      metabolism.
FAU - Sakamoto, Wataru
AU  - Sakamoto W
AD  - Department of Medicine, Stony Brook University, Stony Brook, NY.
AD  - Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
AD  - Exploratory Research Laboratories, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Coant, Nicolas
AU  - Coant N
AD  - Department of Medicine, Stony Brook University, Stony Brook, NY.
AD  - Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
FAU - Canals, Daniel
AU  - Canals D
AUID- ORCID: 0000-0002-9293-5123
AD  - Department of Medicine, Stony Brook University, Stony Brook, NY.
AD  - Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
FAU - Obeid, Lina M
AU  - Obeid LM
AUID- ORCID: 0000-0002-0734-0847
AD  - Department of Medicine, Stony Brook University, Stony Brook, NY.
AD  - Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
AD  - Northport Veterans Affairs Medical Center, Northport, NY.
FAU - Hannun, Yusuf A
AU  - Hannun YA
AUID- ORCID: 0000-0003-3349-3369
AD  - Department of Medicine, Stony Brook University, Stony Brook, NY 
      yusuf.hannun@stonybrookmedicine.edu.
AD  - Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
AD  - Department of Biochemistry, Stony Brook University, Stony Brook, NY.
AD  - Department of Pharmacology, Stony Brook University, Stony Brook, NY.
AD  - Department of Pathology, Stony Brook University, Stony Brook, NY.
LA  - eng
GR  - R01 GM097741/GM/NIGMS NIH HHS/United States
GR  - R01 CA172517/CA/NCI NIH HHS/United States
GR  - R01 CA218678/CA/NCI NIH HHS/United States
GR  - P01 CA097132/CA/NCI NIH HHS/United States
GR  - R35 GM118128/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180828
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Sphingolipids)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - EC 3.5.1.23 (Neutral Ceramidase)
SB  - IM
MH  - Apoptosis/physiology
MH  - Blotting, Western
MH  - Cell Membrane/metabolism
MH  - Cell Survival/physiology
MH  - Colonic Neoplasms/metabolism
MH  - Golgi Apparatus/*metabolism
MH  - HCT116 Cells
MH  - Humans
MH  - Lipid Metabolism/physiology
MH  - Microscopy, Confocal
MH  - Neutral Ceramidase/*metabolism
MH  - Signal Transduction/physiology
MH  - Sphingolipids/metabolism
MH  - Sphingomyelin Phosphodiesterase/metabolism
PMC - PMC6210901
OTO - NOTNLM
OT  - Golgi
OT  - apoptosis
OT  - colon cancer
OT  - neutral ceramidase
OT  - sphingolipids
EDAT- 2018/08/30 06:00
MHDA- 2019/09/03 06:00
PMCR- 2019/11/01
CRDT- 2018/08/30 06:00
PHST- 2018/07/02 00:00 [received]
PHST- 2018/08/28 00:00 [revised]
PHST- 2018/08/30 06:00 [pubmed]
PHST- 2019/09/03 06:00 [medline]
PHST- 2018/08/30 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - S0022-2275(20)30912-3 [pii]
AID - m088187 [pii]
AID - 10.1194/jlr.M088187 [doi]
PST - ppublish
SO  - J Lipid Res. 2018 Nov;59(11):2116-2125. doi: 10.1194/jlr.M088187. Epub 2018 Aug 
      28.