The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide.

Abstract	Sulfatide synthesis in the human renal cancer cell line SMKT-R3 was strongly inhibited in the presence of low µM concentrations of AG-205, a progesterone receptor membrane component 1 (PGRMC1) antagonist. This was also the case in Chinese hamster ovary (CHO) cells stably transfected with UDP-galactose: ceramide galactosyltransferase and cerebroside sulfotransferase, the two enzymes required for sulfatide synthesis. In CHO cells synthesizing galactosylceramide but not sulfatide, galactosylceramide was also strongly reduced, suggesting an effect at the level of galactolipid synthesis. Notably, AG-205 inhibited galactosylceramide synthesis to a similar extent in wild type CHO cells and cells that lack PGRMC1 and/or PGRMC2. In vitro enzyme activity assays showed that AG-205 is an inhibitor of UDP-galactose: ceramide galactosyltransferase, but not cerebroside sulfotransferase. This study shows that PGRMC1 is only one of several targets of AG-205 and should be used with caution, especially in studies using cells synthesizing galactosylceramide and sulfatide.
Authors	Lihua Wang-Eckhardt, Ivonne Becker, Matthias Eckhardt
Journal	Cells (Cells) Vol. 10 Issue 12 (12 13 2021) ISSN: 2073-4409 [Electronic] Switzerland
PMID	34944026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AG 205 Enzyme Inhibitors Galactosylceramides Indoles Membrane Proteins PGRMC1 protein, human PGRMC2 protein, human Receptors, Progesterone Sulfoglycosphingolipids Uridine Diphosphate Galactose N-Acylsphingosine Galactosyltransferase Sulfotransferases galactosylceramide sulfotransferase
Topics	Animals CHO Cells Cricetulus Enzyme Inhibitors (pharmacology) Galactosylceramides (antagonists & inhibitors, biosynthesis) Humans Indoles (pharmacology) Kidney Neoplasms (drug therapy, genetics, pathology) Membrane Proteins (antagonists & inhibitors, genetics) N-Acylsphingosine Galactosyltransferase Receptors, Progesterone (antagonists & inhibitors, genetics) Sulfoglycosphingolipids (antagonists & inhibitors, metabolism) Sulfotransferases (genetics) Uridine Diphosphate Galactose (genetics)

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