Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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
; ; ; ; ; ; and
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
  • pmid:21177474
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
2016-04-01 11:02:20
date last changed
2024-01-07 06:56:47
@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}},
  keywords     = {{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          = {{https://lup.lub.lu.se/search/files/2331004/1766780.pdf}},
  doi          = {{10.1194/jlr.M012880}},
  volume       = {{52}},
  year         = {{2010}},
}