title: Antidepressants attenuate the dexamethasone-induced decrease in viability and proliferation of human neuroblastoma SH-SY5Y cells: a involvement of extracellular regulated kinase (ERK1/2).
abstract: Excessive glucocorticoid levels in depressed patients have been associated with atrophic changes in some brain regions, but only few studies suggest that some antidepressants can interfere with deleterious effect of glucocorticoids on neuronal cells. The aim of the present study was to examine the effect of dexamethasone (DEX), a synthetic glucocorticoid and some antidepressants from different chemical groups (imipramine, desipramine, amitriptyline, citalopram, fluoxetine, reboxetine and tianeptine) on SH-SY5Y cells cultured in the medium containing steroid-free serum. DEX in concentrations from 1 to 100 μM did not change LDH release but exposure to 10 μM and 100 μM DEX for 24, 48 and 72 h caused a significant reduction in cell viability and proliferation as confirmed by MTT reduction and BrdU ELISA assays, respectively. Twenty four-hour incubation of cells with antidepressants (0.05-10 μM) and DEX (10 μM) showed that imipramine, amitriptyline, desipramine, citalopram and fluoxetine at concentrations from 0.1 up to 1 μM, reboxetine (0.1 μM) and tianeptine (0.05 μM) prevented the DEX-induced decreases in cell viability and proliferation rate. The protective effects of antidepressants were ameliorated by inhibitors of MAPK/ERK1/2, but not PI3-K/Akt pathway as shown for imipramine, fluoxetine and reboxetine. Moreover, Western blot analysis showed the decrease in the activated form of ERK1/2 (p-ERK) after DEX treatment and this effect was inhibited by imipramine. Thus, the reduction in SH-SY5Y cell viability caused by DEX appears to be related to its antiproliferative activity and some antidepressant drugs in low concentrations attenuate this effect by mechanism which involves the activation of MAPK/ERK1/2 pathway.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Leskiewicz
authors.forename: D
authors.initials: D
authors.lastname: Jantas
authors.forename: M
authors.initials: M
authors.lastname: Regulska
authors.forename: J
authors.initials: J
authors.lastname: Kaczanowska
authors.forename: A
authors.initials: A
authors.lastname: Basta-Kaim
authors.forename: B
authors.initials: B
authors.lastname: Budziszewska
authors.forename: M
authors.initials: M
authors.lastname: Kubera
authors.forename: W
authors.initials: W
authors.lastname: Lason
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology*
chemical_list: D000928:Antidepressive Agents; D003907:Dexamethasone
keywords: BrdU assay; Fluoxetine; Imipramine; Synthetic glucocorticoid; Tianeptine