title: Participation of prostaglandin D2 in the mobilization of the nuclear-localized CTP:phosphocholine cytidylyltransferase alpha in renal epithelial cells.
abstract: 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 PGD(2). In this work we found that Indo induced CCTα distribution into intranuclear Lamin A/C foci. Exogenous PGD(2) reverted this effect by inducing CCTα redistribution to nuclear envelope, suggesting that PGD(2) maintains PC synthesis by CCTα mobilization. Interestingly, we found that the effect of PGD(2) 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, PGD(2), by modulating CCTα intracellular location.
authors.affiliation: Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina.
authors.forename: Nicolás O
authors.initials: NO
authors.lastname: Favale
authors.affiliation: Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina.
authors.forename: Lucila G
authors.initials: LG
authors.lastname: Pescio
authors.affiliation: Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina.
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Santacreu
authors.affiliation: Instituto de Investigaciones en Ciencias de la Salud Humana (IICSHUM), Universidad Nacional de La Rioja, La Rioja, Argentina.
authors.forename: María G
authors.initials: MG
authors.lastname: Márquez
authors.affiliation: LANAIS-PROEM-IQUIFIB-CONICET, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina. Electronic address: speziale@ffyb.uba.ar.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Sterin-Speziale
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008297:Male; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D009685:Nuclear Envelope / Q000201:enzymology*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C480283:CTP phosphocholine cytidylyltransferase, alpha isoform, rat; D019916:Choline-Phosphate Cytidylyltransferase; D015230:Prostaglandin D2; D007213:Indomethacin
keywords: CTP:phosphocholine cytidylyltransferase alpha; ERK1/2; Enzyme distribution changes; Nuclear localization; Prostaglandin D(2)