Advanced

Expression of intestinal and lung alkaline sphingomyelinase and neutral ceramidase in cystic fibrosis f508del transgenic mice.

Ohlsson, Lena LU ; Hjelte, Lena; Hühn, Michael; Scholte, Bob J; Wilke, Martina; Flodström-Tullberg, Malin and Nilsson, Åke LU (2008) In Journal of Pediatric Gastroenterology and Nutrition - Jpgn 47(5). p.547-554
Abstract
OBJECTIVES: The intestinal brush border enzymes alkaline sphingomyelinase (alk-SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition, alk-SMase, CDase, and acid sphingomyelinase (acid-SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF. MATERIALS AND METHODS: We used mice with F508del (Cftr) mutation, a CF mouse model with well-characterized intestinal pathology. Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intestinal contents of wild-type mice, homozygous,... (More)
OBJECTIVES: The intestinal brush border enzymes alkaline sphingomyelinase (alk-SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition, alk-SMase, CDase, and acid sphingomyelinase (acid-SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF. MATERIALS AND METHODS: We used mice with F508del (Cftr) mutation, a CF mouse model with well-characterized intestinal pathology. Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intestinal contents of wild-type mice, homozygous, and heterozygous F508del mice. RESULTS: No difference was found in levels of CDase and alk-SMase in the small intestinal mucosa or in their longitudinal distribution. Acid-SMase activity was significantly lower in the mucosa of the distal half of the small intestine of F508del compared with wild-type mice. Despite a lower body weight of F508del mice, length and weight of the small intestine and weight per centimeter of colon were larger than in wild-type. Neutral CDase and alk-SMase activities in lungs were lower than in the gut, whereas acid-SMase activity was comparable in both organs. CDase activity in the spleen was significantly higher in F508del than in wild-type mice. CONCLUSIONS: Alk-SMase and neutral CDase are normally expressed in F508del CF mice, whereas activity of acid-SMase in the distal small intestine is decreased. We found no differences in activity of these enzymes in lungs in this mouse model. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Pediatric Gastroenterology and Nutrition - Jpgn
volume
47
issue
5
pages
547 - 554
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000260519400003
  • pmid:18955860
  • scopus:59849088539
ISSN
1536-4801
DOI
10.1097/MPG.0b013e3181826daf
language
English
LU publication?
yes
id
80c65245-9f04-4e16-a6d8-f09cb31a38d9 (old id 1261874)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18955860?dopt=Abstract
date added to LUP
2008-11-04 11:31:30
date last changed
2017-02-12 03:27:34
@article{80c65245-9f04-4e16-a6d8-f09cb31a38d9,
  abstract     = {OBJECTIVES: The intestinal brush border enzymes alkaline sphingomyelinase (alk-SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition, alk-SMase, CDase, and acid sphingomyelinase (acid-SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF. MATERIALS AND METHODS: We used mice with F508del (Cftr) mutation, a CF mouse model with well-characterized intestinal pathology. Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intestinal contents of wild-type mice, homozygous, and heterozygous F508del mice. RESULTS: No difference was found in levels of CDase and alk-SMase in the small intestinal mucosa or in their longitudinal distribution. Acid-SMase activity was significantly lower in the mucosa of the distal half of the small intestine of F508del compared with wild-type mice. Despite a lower body weight of F508del mice, length and weight of the small intestine and weight per centimeter of colon were larger than in wild-type. Neutral CDase and alk-SMase activities in lungs were lower than in the gut, whereas acid-SMase activity was comparable in both organs. CDase activity in the spleen was significantly higher in F508del than in wild-type mice. CONCLUSIONS: Alk-SMase and neutral CDase are normally expressed in F508del CF mice, whereas activity of acid-SMase in the distal small intestine is decreased. We found no differences in activity of these enzymes in lungs in this mouse model.},
  author       = {Ohlsson, Lena and Hjelte, Lena and Hühn, Michael and Scholte, Bob J and Wilke, Martina and Flodström-Tullberg, Malin and Nilsson, Åke},
  issn         = {1536-4801},
  language     = {eng},
  number       = {5},
  pages        = {547--554},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Pediatric Gastroenterology and Nutrition - Jpgn},
  title        = {Expression of intestinal and lung alkaline sphingomyelinase and neutral ceramidase in cystic fibrosis f508del transgenic mice.},
  url          = {http://dx.doi.org/10.1097/MPG.0b013e3181826daf},
  volume       = {47},
  year         = {2008},
}