PMID- 14557071
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20190708
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 315
DP  - 2003 Oct 2
TI  - Neutral ceramidase gene: role in regulating ceramide-induced apoptosis.
PG  - 113-22
AB  - The sphingolipid, ceramide, is a natural dietary constituent and a potent 
      mediator of apoptosis. If left undegraded, it may induce apoptosis and cause 
      disruption of cellular integrity. A potential mechanism to prevent 
      ceramide-induced apoptosis in various organs may involve ceramidases that 
      facilitate the degradation of ceramide. In this study, we first isolated and 
      characterized the murine neutral ceramidase (N-CDase) gene, mapped its 
      chromosomal location and determined its developmental and organ-specific 
      expression. Then we used cultured mesangial cells as our in vitro model and mouse 
      gastrointestinal (GI) tract as the in vivo model to determine the effects of an 
      inhibitor of N-CDase, D-erythro-MAPP, to delineate whether N-CDase plays a role 
      in preventing ceramide-induced apoptosis. Our results show that: (i) the 
      structure of the murine neutral ceramidase gene is virtually identical to that of 
      the human gene; (ii) it is localized on chromosome 19 at bands C2-C3 that is 
      syntenic to human chromosome 10q24-26; (iii) N-CDase expression is 
      developmentally regulated and it is expressed at high levels in cultured 
      mesangial cells and in specific regions of the mouse small intestine; (iv) 
      inhibition of N-CDase by D-erythro-MAPP leads to increased ceramide levels and 
      consequent apoptosis in cultured mesangial cells; (v) mice treated with 
      D-erythro-MAPP alone also caused apoptosis in the small intestine; and (vi) mice 
      treated with D-erythro-MAPP prior to feeding C2 ceramide manifest markedly 
      elevated levels of apoptosis in the GI tract raising the possibility that neutral 
      ceramidase plays a detoxifying role against inadvertent stimulation of 
      ceramide-induced apoptosis in organs that come in contact with this sphingolipid. 
      We propose that N-CDase is an essential component of an innate detoxifying 
      mechanism to prevent ceramide-induced apoptosis.
FAU - Choi, Moonsuk S
AU  - Choi MS
AD  - Section on Developmental Genetics, Heritable Disorders Branch, The National 
      Institute of Child Health and Human Development, The National Institutes of 
      Health, Room 9S241, Building 10, Bethesda, MD 20892-1830, USA.
FAU - Anderson, Mary A
AU  - Anderson MA
FAU - Zhang, Zhongjian
AU  - Zhang Z
FAU - Zimonjic, Drazen B
AU  - Zimonjic DB
FAU - Popescu, Nicolae
AU  - Popescu N
FAU - Mukherjee, Anil B
AU  - Mukherjee AB
LA  - eng
SI  - GENBANK/AY049008
PT  - Journal Article
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Ceramides)
RN  - 0 (Myristates)
RN  - 0 (Propanolamines)
RN  - 0 (RNA, Messenger)
RN  - 60847-25-8 (2-(N-myristoylamino)-1-phenyl-1-propanol)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.23 (ASAH2 protein, human)
RN  - EC 3.5.1.23 (Asah2 protein, mouse)
RN  - EC 3.5.1.23 (Ceramidases)
RN  - EC 3.5.1.23 (Neutral Ceramidase)
SB  - IM
MH  - Amidohydrolases/antagonists & inhibitors/*genetics/physiology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Line
MH  - Ceramidases
MH  - Ceramides/metabolism/*pharmacology
MH  - Chromosome Mapping
MH  - Dose-Response Relationship, Drug
MH  - Exons
MH  - Gene Expression
MH  - Gene Expression Regulation, Developmental
MH  - Gene Expression Regulation, Enzymologic
MH  - Genes/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - In Situ Nick-End Labeling
MH  - Introns
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/enzymology
MH  - Molecular Sequence Data
MH  - Myristates/pharmacology
MH  - Neutral Ceramidase
MH  - Propanolamines/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Sequence Analysis, DNA
EDAT- 2003/10/15 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/10/15 05:00
PHST- 2003/10/15 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/10/15 05:00 [entrez]
AID - S0378111903007212 [pii]
AID - 10.1016/s0378-1119(03)00721-2 [doi]
PST - ppublish
SO  - Gene. 2003 Oct 2;315:113-22. doi: 10.1016/s0378-1119(03)00721-2.