Next Article in Journal
Advances in Biomarkers for PCa Diagnostics and Prognostics—A Way towards Personalized Medicine
Next Article in Special Issue
Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry
Previous Article in Journal
Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and the 2016 WHO Classification
Previous Article in Special Issue
E-Learning for Rare Diseases: An Example Using Fabry Disease
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(10), 2192; doi:10.3390/ijms18102192

Glucosylsphingosine Causes Hematological and Visceral Changes in Mice—Evidence for a Pathophysiological Role in Gaucher Disease

1
Albrecht-Kossel Institute of the Rostock University Medical Center, 18147 Rostock, Germany
2
Centogene AG, 18057 Rostock, Germany
3
Department of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany
4
Institute for Medical Psychology and Medical Sociology, Rostock University Medical Center, 18147 Rostock, Germany
*
Author to whom correspondence should be addressed.
Received: 8 September 2017 / Revised: 26 September 2017 / Accepted: 9 October 2017 / Published: 20 October 2017
(This article belongs to the Special Issue Rare Diseases: Molecular Mechanisms and Therapeutic Strategies)
View Full-Text   |   Download PDF [8101 KB, uploaded 20 October 2017]   |  

Abstract

Glucosylceramide and glucosylsphingosine are the two major storage products in Gaucher disease (GD), an inherited metabolic disorder caused by a deficiency of the lysosomal enzyme glucocerebrosidase. The build-up of glucosylceramide in the endoplasmic reticulum and prominent accumulation in cell lysosomes of tissue macrophages results in decreased blood cell and platelet counts, and skeletal abnormalities. The pathological role of the deacylated form of glucosylceramide, glucosylsphingosine (lyso-Gb1), a recently identified sensitive and specific biomarker for GD, is not well investigated. We established a long-term infusion model in C57BL/6JRj mice to examine the effect of lyso-Gb1 on representative hallmark parameters of GD. Mice received lyso-Gb1 at a dosage of 10 mg·kg−1 per day as a continuous subcutaneous administration, and were routinely checked for blood lyso-Gb1 levels using liquid chromatography-multiple reaction monitoring mass spectrometry (LC/MRM-MS) measurements at four-weekly intervals throughout treatment. The C57BL/6JRj mice showed a stable increase of lyso-Gb1 up to->500-fold greater than the normal reflecting concentrations seen in moderately to severely affected patients. Furthermore, lyso-Gb1 accumulated in peripheral tissues. The mice developed hematological symptoms such as reduced hemoglobin and hematocrit, increased spleen weights and a slight inflammatory tissue response after eight weeks of treatment. The above findings indicate a measurable visceral and hematological response in treated mice that suggests a role for lyso-Gb1 in the development of peripheral signs of GD. View Full-Text
Keywords: sphingolipids; glucocerebrosidase; biomarker; storage disease pathology; chemically-induced phenotype sphingolipids; glucocerebrosidase; biomarker; storage disease pathology; chemically-induced phenotype
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lukas, J.; Cozma, C.; Yang, F.; Kramp, G.; Meyer, A.; Neßlauer, A.-M.; Eichler, S.; Böttcher, T.; Witt, M.; Bräuer, A.U.; Kropp, P.; Rolfs, A. Glucosylsphingosine Causes Hematological and Visceral Changes in Mice—Evidence for a Pathophysiological Role in Gaucher Disease. Int. J. Mol. Sci. 2017, 18, 2192.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top