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

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-galacto...

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Autores principales: Wang-Eckhardt, Lihua, Becker, Ivonne, Eckhardt, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700550/
https://www.ncbi.nlm.nih.gov/pubmed/34944026
http://dx.doi.org/10.3390/cells10123520
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author Wang-Eckhardt, Lihua
Becker, Ivonne
Eckhardt, Matthias
author_facet Wang-Eckhardt, Lihua
Becker, Ivonne
Eckhardt, Matthias
author_sort Wang-Eckhardt, Lihua
collection PubMed
description 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.
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spelling pubmed-87005502021-12-24 The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide Wang-Eckhardt, Lihua Becker, Ivonne Eckhardt, Matthias Cells Article 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. MDPI 2021-12-13 /pmc/articles/PMC8700550/ /pubmed/34944026 http://dx.doi.org/10.3390/cells10123520 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang-Eckhardt, Lihua
Becker, Ivonne
Eckhardt, Matthias
The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title_full The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title_fullStr The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title_full_unstemmed The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title_short The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide
title_sort pgrmc1 antagonist ag-205 inhibits synthesis of galactosylceramide and sulfatide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700550/
https://www.ncbi.nlm.nih.gov/pubmed/34944026
http://dx.doi.org/10.3390/cells10123520
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