Participation of prostaglandin D2 in the mobilization of the nuclear-localized CTP:phosphocholine cytidylyltransferase alpha in renal epithelial cells

• Published in: Biochimica et biophysica acta Vol. 1861; no. 6; pp. 513 - 523
• Main Authors: Favale, Nicolás O., Pescio, Lucila G., Santacreu, Bruno J., Márquez, María G., Sterin-Speziale, Norma B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2016
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Blotting, Western; Cell Nucleus - enzymology; Cells, Cultured; Choline-Phosphate Cytidylyltransferase - metabolism; CTP:phosphocholine cytidylyltransferase alpha; Enzyme Activation - drug effects; Enzyme distribution changes; Epithelial Cells - drug effects; Epithelial Cells - metabolism; ERK1/2; Indomethacin - pharmacology; Kidney - cytology; Male; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Models, Biological; Nuclear Envelope - enzymology; Nuclear localization; Prostaglandin D2; Prostaglandin D2 - pharmacology; Protein Transport - drug effects; Rats, Wistar; ERK1/2; Nuclear localization; Prostaglandin D2; CTP:phosphocholine cytidylyltransferase alpha; Enzyme distribution changes; Prostaglandin D
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2016.03.025

Phosphatidylcholine (PC) is the main constituent of mammalian cell membranes. Consequently, preservation of membrane PC content and composition — PC homeostasis — is crucial to maintain cellular life. PC biosynthetic pathway is generally controlled by CTP:phosphocholine cytidylyltransferase (CCT), which is considered the rate-limiting enzyme. CCTα is an amphitropic protein, whose enzymatic activity is commonly associated with endoplasmic reticulum redistribution. However, most of the enzyme is located inside the nuclei. Here, we demonstrate that CCTα is the most abundant isoform in renal collecting duct cells, and its redistribution is dependent on endogenous prostaglandins. Previously we have demonstrated that PC synthesis was inhibited by indomethacin (Indo) treatment, and this effect was reverted by exogenous PGD2. In this work we found that Indo induced CCTα distribution into intranuclear Lamin A/C foci. Exogenous PGD2 reverted this effect by inducing CCTα redistribution to nuclear envelope, suggesting that PGD2 maintains PC synthesis by CCTα mobilization. Interestingly, we found that the effect of PGD2 was dependent on ERK1/2 activation. In conclusion, our previous observations and the present results lead us to suggest that papillary cells possess the ability to maintain their structural integrity through the synthesis of their own survival molecule, PGD2, by modulating CCTα intracellular location. •Indomethacin induces CCTα distribution to intranuclear Lamin A/C foci.•Exogenous PGD2 induces CCTα distribution to nuclear envelope from intranuclear Lamin A/C foci.•The effect of PGD2 on CCTα distribution depends on ERK1/2 activation.