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Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: A study on the enzyme knockout mice.

Zhang, Yao LU ; Cheng, Yajun LU ; Hansen, Gert H; Niels-Christiansen, Lise-Lotte; Koentgen, Frank; Ohlsson, Lena LU ; Nilsson, Åke LU and Duan, Rui-Dong LU (2010) In Journal of Lipid Research 52(4). p.771-781
Abstract
Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by Cre-LoxP system and studied SM digestion. Both wild type (WT) and the KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum and liver were analysed by TLC. In KO mice, non-digested 3H-SM in the intestinal content increased by 6 fold and the formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H-ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was decreased by 95%. After three hours, a small increase in 3H-ceramide was... (More)
Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by Cre-LoxP system and studied SM digestion. Both wild type (WT) and the KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum and liver were analysed by TLC. In KO mice, non-digested 3H-SM in the intestinal content increased by 6 fold and the formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H-ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was decreased by 95%. After three hours, a small increase in 3H-ceramide was identified in distal intestine in KO mice. In feces 3H-SM was increased by 243% and ceramide decreased by 74% in the KO mice. The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore alkaline phosphatase activity in the mucosa was reduced by 50%, and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. The study provides definite proofs for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
NPP7, alkaline phosphatase, hypertrophy
in
Journal of Lipid Research
volume
52
issue
4
pages
771 - 781
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:21177474
  • wos:000288239300016
  • scopus:79953322390
ISSN
1539-7262
DOI
10.1194/jlr.M012880
language
English
LU publication?
yes
id
26923b62-ebe5-4229-b1dd-3851dd24dd37 (old id 1755883)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21177474?dopt=Abstract
date added to LUP
2011-01-03 18:25:18
date last changed
2018-05-29 10:57:42
@article{26923b62-ebe5-4229-b1dd-3851dd24dd37,
  abstract     = {Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by Cre-LoxP system and studied SM digestion. Both wild type (WT) and the KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum and liver were analysed by TLC. In KO mice, non-digested 3H-SM in the intestinal content increased by 6 fold and the formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H-ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was decreased by 95%. After three hours, a small increase in 3H-ceramide was identified in distal intestine in KO mice. In feces 3H-SM was increased by 243% and ceramide decreased by 74% in the KO mice. The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore alkaline phosphatase activity in the mucosa was reduced by 50%, and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. The study provides definite proofs for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function.},
  author       = {Zhang, Yao and Cheng, Yajun and Hansen, Gert H and Niels-Christiansen, Lise-Lotte and Koentgen, Frank and Ohlsson, Lena and Nilsson, Åke and Duan, Rui-Dong},
  issn         = {1539-7262},
  keyword      = {NPP7,alkaline phosphatase,hypertrophy},
  language     = {eng},
  number       = {4},
  pages        = {771--781},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Journal of Lipid Research},
  title        = {Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: A study on the enzyme knockout mice.},
  url          = {http://dx.doi.org/10.1194/jlr.M012880},
  volume       = {52},
  year         = {2010},
}