Sphingosine kinase and sphingosine-1phosphate regulate epithelial cell architecture by the modulation of de novo sphingolipid synthesis

Autor: Daniela Judith Romero, Gerardo Raul Corradi, Nicolás Octavio Favale, Lucila Gisele Pescio, Norma B. Sterin-Speziale, Bruno Jaime Santacreu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Thin-Layer Chromatography
0301 basic medicine
Cellular differentiation
Hypertonic Solutions
Sphingosine kinase
CELL DIFFERENTIATION
Biochemistry
Epithelium
Madin Darby Canine Kidney Cells
purl.org/becyt/ford/1 [https]
chemistry.chemical_compound
Contractile Proteins
0302 clinical medicine
Cell Movement
Sphingosine
Animal Cells
Medicine and Health Sciences
Small interfering RNAs
Enzyme Inhibitors
RNA
Small Interfering
SPHINGOLIPID
Cytoskeleton
Multidisciplinary
Chromatographic Techniques
Cell Differentiation
Adherens Junctions
Lipids
Cell biology
Nucleic acids
Phosphotransferases (Alcohol Group Acceptor)
030220 oncology & carcinogenesis
Medicine
lipids (amino acids
peptides
and proteins)
Cellular Types
Anatomy
Cellular Structures and Organelles
Signal transduction
MDCK
Signal Transduction
Research Article
Cell Physiology
Ceramide
Science
Research and Analysis Methods
S1P
Adherens junction
03 medical and health sciences
Dogs
Genetics
Animals
Sphingosine-1-phosphate
Non-coding RNA
purl.org/becyt/ford/1.6 [https]
Cell Proliferation
Sphingolipids
Cell growth
Biology and Life Sciences
Proteins
Epithelial Cells
Cell Biology
Sphingolipid
Actins
Cell Metabolism
Gene regulation
Planar Chromatography
Cytoskeletal Proteins
Biological Tissue
030104 developmental biology
chemistry
RNA
Snail Family Transcription Factors
Gene expression
Lysophospholipids
Developmental Biology
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
PLoS ONE, Vol 14, Iss 3, p e0213917 (2019)
PLoS ONE
DOI: 10.1371/journal.pone.0213917
Popis: Sphingolipids regulate several aspects of cell behavior and it has been demonstrated that cells adjust their sphingolipid metabolism in response to metabolic needs. Particularly, sphingosine-1-phosphate (S1P), a final product of sphingolipid metabolism, is a potent bioactive lipid involved in the regulation of various cellular processes, including cell proliferation, cell migration, actin cytoskeletal reorganization and cell adhesion. In previous work in rat renal papillae, we showed that sphingosine kinase (SK) expression and S1P levels are developmentally regulated and control de novo sphingolipid synthesis. The aim of the present study was to evaluate the participation of SK/S1P pathway in the triggering of cell differentiation by external hypertonicity. We found that hypertonicity evoked a sharp decrease in SK expression, thus activating the de novo sphingolipid synthesis pathway. Furthermore, the inhibition of SK activity evoked a relaxation of cell-cell adherens junction (AJ) with accumulation of the AJ complex (E-cadherin/β-catenin/α-catenin) in the Golgi complex, preventing the acquisition of the differentiated cell phenotype. This phenotype alteration was a consequence of a sphingolipid misbalance with an increase in ceramide levels. Moreover, we found that SNAI1 and SNAI2 were located in the cell nucleus with impairment of cell differentiation induced by SK inhibition, a fact that is considered a biochemical marker of epithelial to mesenchymal transition. So, we suggest that the expression and activity of SK1, but not SK2, act as a control system, allowing epithelial cells to synchronize the various branches of sphingolipid metabolism for an adequate cell differentiation program. Fil: Santacreu, Bruno Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Pescio, Lucila Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Romero, Daniela Judith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Celular y Molecular; Argentina Fil: Corradi, Gerardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Sterin, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Favale, Nicolas Octavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Databáze: OpenAIRE
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