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Research ArticleArticle

Inhibition of CTP:Phosphocholine Cytidylyltransferase by C2-Ceramide and Its Relationship to Apoptosis

Belén Ramos, Mohammed El Mouedden, Enrique Claro and Suzanne Jackowski
Molecular Pharmacology November 2002, 62 (5) 1068-1075; DOI: https://doi.org/10.1124/mol.62.5.1068
Belén Ramos
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Mohammed El Mouedden
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Enrique Claro
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Suzanne Jackowski
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Abstract

Apoptosis induced by antitumor phospholipid analogs takes place after the inhibition of the CTP:phosphocholine cytidylyltransferase (CCT; EC 2.7.7.15) catalyzed step of phosphatidylcholine (PtdCho) biosynthesis. Exposure of cells to synthetic short-chain ceramide analogs also triggers apoptosis concomitant with decreased PtdCho biosynthesis, and the present study was undertaken to ascertain whether C2-ceramide inhibition of PtdCho synthesis is direct or secondary to other ceramide-mediated cellular responses. The exposure of COS-7 cells to either C2-ceramide, ET-18-OCH3, or farnesol resulted in time- and dose-dependent apoptotic cell death. Cells treated with C2-ceramide or ET-18-OCH3 selectively and immediately accumulated phosphocholine, whereas CDP-choline increased with farnesol treatment. In vitro assays of CCT activity demonstrated that C2-ceramide directly inhibited CCT. Comparison of different N-linked sphingosine derivatives suggests an inverse relationship between the length of the N-linked carbon chain and the derivatives ability to trigger apoptosis and inhibit CCT. Taken together, our results suggest CCT as a primary target for C2-ceramide inhibition that accounts for its cytotoxic effects.

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Molecular Pharmacology: 62 (5)
Molecular Pharmacology
Vol. 62, Issue 5
1 Nov 2002
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Research ArticleArticle

Inhibition of CTP:Phosphocholine Cytidylyltransferase by C2-Ceramide and Its Relationship to Apoptosis

Belén Ramos, Mohammed El Mouedden, Enrique Claro and Suzanne Jackowski
Molecular Pharmacology November 1, 2002, 62 (5) 1068-1075; DOI: https://doi.org/10.1124/mol.62.5.1068

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Research ArticleArticle

Inhibition of CTP:Phosphocholine Cytidylyltransferase by C2-Ceramide and Its Relationship to Apoptosis

Belén Ramos, Mohammed El Mouedden, Enrique Claro and Suzanne Jackowski
Molecular Pharmacology November 1, 2002, 62 (5) 1068-1075; DOI: https://doi.org/10.1124/mol.62.5.1068
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