Phosphatidylcholine metabolism is altered in a monocyte-derived macrophage model of Gaucher disease but not in lymphocytes.
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-14C]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 [3H]GlcCer accumulation. Moreover, metabolic labeling with L-[3-3H]serine and L-[methyl-3H]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.
Trajkovic-Bodennec
Selena
S
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Bodennec
Jacques
J
Futerman
Anthony H
AH
D002247:Carbon Isotopes; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D003903:Deuterium; D005776:Gaucher Disease / Q000378:metabolism*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors; D005963:Glucosylceramides / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D010713:Phosphatidylcholines / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D015854:Up-Regulation
D002247:Carbon Isotopes; D005963:Glucosylceramides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D007294:Inositol; D003903:Deuterium; D005962:Glucosylceramidase; C011423:conduritol epoxide