title: Sphingomyelin metabolism is involved in the differentiation of MDCK cells induced by environmental hypertonicity.
abstract: Sphingolipids (SLs) are relevant lipid components of eukaryotic cells. Besides regulating various cellular processes, SLs provide the structural framework for plasma membrane organization. Particularly, SM is associated with detergent-resistant microdomains. We have previously shown that the adherens junction (AJ) complex, the relevant cell-cell adhesion structure involved in cell differentiation and tissue organization, is located in an SM-rich membrane lipid domain. We have also demonstrated that under hypertonic conditions, Madin-Darby canine kidney (MDCK) cells acquire a differentiated phenotype with changes in SL metabolism. For these reasons, we decided to evaluate whether SM metabolism is involved in the acquisition of the differentiated phenotype of MDCK cells. We found that SM synthesis mediated by SM synthase 1 is involved in hypertonicity-induced formation of mature AJs, necessary for correct epithelial cell differentiation. Inhibition of SM synthesis impaired the acquisition of mature AJs, evoking a disintegration-like process reflected by the dissipation of E-cadherin and β- and α-catenins from the AJ complex. As a consequence, MDCK cells did not develop the hypertonicity-induced differentiated epithelial cell phenotype.
authors: Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina IQUIFIB-LANAIS-PROEM-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
authors: Nicolás Octavio
authors: NO
authors: Favale
authors: Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina IQUIFIB-LANAIS-PROEM-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
authors: Bruno Jaime
authors: BJ
authors: Santacreu
authors: Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina IQUIFIB-LANAIS-PROEM-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
authors: Lucila Gisele
authors: LG
authors: Pescio
authors: IQUIFIB-LANAIS-PROEM-CONICET, Ciudad Autónoma de Buenos Aires, Argentina Instituto de Investigaciones en Ciencias de la Salud Humana (IICSHUM), Universidad Nacional de La Rioja , La Rioja, Argentina.
authors: Maria Gabriela
authors: MG
authors: Marquez
authors: IQUIFIB-LANAIS-PROEM-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
authors: Norma Beatriz
authors: NB
authors: Sterin-Speziale
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D061985:Madin Darby Canine Kidney Cells; D009997:Osmotic Pressure; D010641:Phenotype; D013109:Sphingomyelins / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D004791:Enzyme Inhibitors; D013109:Sphingomyelins; D051178:alpha Catenin; D051176:beta Catenin; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase
keywords: Madin-Darby canine kidney cells; renal epithelial cells; sphingomyelin synthase