title: Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells.
abstract: Osmotic changes occur in many tissues and profoundly influence cell function. Herein, we investigated the effect of hyperosmotic stress on retinal pigmented epithelial (RPE) cells using a microarray approach. Upon 4-h exposure to 100 mM NaCl or 200 mM sucrose, 79 genes were downregulated and 72 upregulated. Three gene ontology categories were significantly modulated: cell proliferation, transcription from RNA polymerase II promoter and response to abiotic stimulus. Fluorescent-activated cell sorting analysis further demonstrated that owing to hyperosmotic stimulation for 24 h, cell count and cell proliferation, as well as the percentage of cells in G0/G1 and S phases were significantly decreased, whereas the percentage of cells in G2/M phases increased, and apoptosis and necrosis remained unaffected. Accordingly, hyperosmotic conditions induced a decrease of cyclin B1 and D1 expression, and an activation of the p38 mitogen-activated protein kinase. In conclusion, our results demonstrate that hypertonic conditions profoundly affect RPE cell gene transcription regulating cell proliferation by downregulation cyclin D1 and cyclin B1 protein expression.
authors.affiliation: Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Arsenijevic
authors.forename: A
authors.initials: A
authors.lastname: Vujovic
authors.forename: F
authors.initials: F
authors.lastname: Libert
authors.forename: A
authors.initials: A
authors.lastname: Op de Beeck
authors.forename: A
authors.initials: A
authors.lastname: Hébrant
authors.forename: S
authors.initials: S
authors.lastname: Janssens
authors.forename: F
authors.initials: F
authors.lastname: Grégoire
authors.forename: A
authors.initials: A
authors.lastname: Lefort
authors.forename: N
authors.initials: N
authors.lastname: Bolaky
authors.forename: J
authors.initials: J
authors.lastname: Perret
authors.forename: L
authors.initials: L
authors.lastname: Caspers
authors.forename: F
authors.initials: F
authors.lastname: Willermain
authors.forename: C
authors.initials: C
authors.lastname: Delporte
mesh_terms: D059447:Cell Cycle Checkpoints; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D063990:Gene Ontology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009997:Osmotic Pressure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D012965:Sodium Chloride / Q000494:pharmacology; D013312:Stress, Physiological; D059467:Transcriptome; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012965:Sodium Chloride; D048051:p38 Mitogen-Activated Protein Kinases