Journal
BLOOD CELLS MOLECULES AND DISEASES
Volume 33, Issue 1, Pages 77-82Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bcmd.2004.03.001
Keywords
lysosomal storage disorder; Gaucher disease; glucosylceramide; glucosylsphingosine; macrophage; phospholipid
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Gaucher disease is caused by defective activity of acid-beta-glucosidase (GlcCerase), resulting in accumulation of glucosylceramide (GlcCer) mainly in macrophages. We now demonstrate that secondary biochemical pathways regulating levels of phospholipid metabolism are altered in a Gaucher disease macrophage model. Upon treatment of macrophages with the GlcCerase inhibitor, conduritol-B-epoxide, phosphatidylcholine (PC) labeling with the metabolic precursor, [methyl-C-14] choline, was elevated after 6 or 12 days in macrophages but not in lymphocytes. These changes correlated with increases in the cytoplasmic/nuclear ratio and with levels of [H-3]GlcCer accumulation. Moreover, metabolic labeling with L-[3-H-3]serine and L-[methyl-H-3]methionine demonstrated that PC synthesis via the methylation of phosphatidylethanolamine is also increased in CBE-treated macrophages. Since PC is a major structural component of biological membranes and the source of various second messengers, we suggest that changes in its metabolism in macrophages may be relevant for understanding Gaucher disease pathology. (C) 2004 Elsevier Inc. All rights reserved.
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