Changes in macrophage morphology in a Gaucher disease model are dependent on CTP:phosphocholine cytidylyltransferase α
We have recently shown that phosphatidylcholine (PC) metabolism is altered in a macrophage model of Gaucher disease. We now demonstrate that treatment of macrophages with conduritol-B-epoxide (CBE), a glucocerebrosidase inhibitor, results in elevated activity of CTP:phosphocholine cytidylyltransfera...
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| Veröffentlicht in: | Blood cells, molecules, & diseases molecules, & diseases, 2007-07, Vol.39 (1), p.124-129 |
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| container_title | Blood cells, molecules, & diseases |
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| creator | Kacher, Yaacov Golan, Avner Pewzner-Jung, Yael Futerman, Anthony H. |
| description | We have recently shown that phosphatidylcholine (PC) metabolism is altered in a macrophage model of Gaucher disease. We now demonstrate that treatment of macrophages with conduritol-B-epoxide (CBE), a glucocerebrosidase inhibitor, results in elevated activity of CTP:phosphocholine cytidylyltransferase (CCT), the rate-limiting enzyme in the pathway of PC biosynthesis. Furthermore, we provide evidence for a role for CCT in Gaucher macrophage growth by using macrophages derived from a genetically modified mouse which lacks a specific CCT isoform, CCTα, in macrophages. Upon CBE-treatment, macrophage size, analyzed by microscopy and by FACS, was significantly increased in macrophages from control mice, but did not increase, or increased to a much lower extent, in CCTα−/− macrophages. Together, these results suggest that the increase in PC biosynthesis is mediated via CCTα, and suggests a possible role for macrophage CCTα in Gaucher disease pathology. |
| doi_str_mv | 10.1016/j.bcmd.2007.03.005 |
| format | Article |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Cell Size - drug effects Cells, Cultured Choline-Phosphate Cytidylyltransferase - biosynthesis Choline-Phosphate Cytidylyltransferase - deficiency CTP:phosphocholine cytidylyltransferase Disease Models, Animal Enzyme Inhibitors - pharmacology Gaucher disease Gaucher Disease - enzymology Gaucher Disease - genetics Gaucher Disease - pathology Glucosylceramidase - antagonists & inhibitors Humans Inositol - analogs & derivatives Inositol - pharmacology Macrophages Macrophages - enzymology Mice Mice, Knockout Phosphatidylcholines - biosynthesis Phospholipid |
| title | Changes in macrophage morphology in a Gaucher disease model are dependent on CTP:phosphocholine cytidylyltransferase α |
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