title: Long-term exposure to low lithium concentrations stimulates proliferation, modifies stress protein expression pattern and enhances resistance to oxidative stress in SH-SY5Y cells.
abstract: SH-SY5Y cells, derived from a human neuroblastoma, were submitted to short- or long-term exposures to lithium carbonate concentrations ranging from 0.5 to 8 mM. Short-term exposures (4 days) to concentrations higher than 6 mM were found to reduce cell growth rate while exposure to 8 mM resulted in significant cell mortality. These ranges of concentrations induced an overexpression of (1) the HSP27 stress protein, (2) a 108 kDa protein (P108) recognized by an anti-phospho-HSP27(Ser78) antibody, and probably corresponding to a phosphorylated HSP27 tetramer, (3) a 105 kDa protein (P105), possible glycosylated or phosphorylated form of the GRP94 stress protein and (4) a phosphorylated (inactivated) form of glycogen synthase kinase (GSK3alpha/beta) SH-SY5Y cells, when cultured in the presence of 0.5 mM lithium for 25 weeks, displayed interesting features as compared to controls: (1) higher cell growth rate, (2) increased resistance toward the inhibitory effects of high lithium concentrations on cell proliferation, (3) lower basal level of lipid peroxidation (TBARS) and improved tolerance to oxidative stress induced by high lithium concentrations, (5) reduced expression of monomeric HSP27 versus an increase of corresponding tetrameric protein (P108) and (6) overexpression of a 105 kDa protein (P105). In conclusion, our study suggests that chronic treatment (over several months) by therapeutic relevant lithium concentrations could favour neurogenesis, decrease the vulnerability of neuronal cells to oxidative stress and induce posttranslational changes of molecular chaperones.
authors.affiliation: Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine Purpan, Université Paul Sabatier Toulouse III, 37 Allées Jules Guesde, 31073 Toulouse, France.
authors.forename: M S
authors.initials: MS
authors.lastname: Allagui
authors.forename: R
authors.initials: R
authors.lastname: Nciri
authors.forename: M F
authors.initials: MF
authors.lastname: Rouhaud
authors.forename: J C
authors.initials: JC
authors.lastname: Murat
authors.forename: A
authors.initials: A
authors.lastname: El Feki
authors.forename: F
authors.initials: F
authors.lastname: Croute
authors.forename: C
authors.initials: C
authors.lastname: Vincent
mesh_terms: D018692:Antimanic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000096:biosynthesis; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D016651:Lithium Carbonate / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D050883:HSC70 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D018696:Neuroprotective Agents; C053387:endoplasmin; D016651:Lithium Carbonate; D038362:Glycogen Synthase Kinase 3