1. Induction of C/EBP beta and GADD153 expression by dopamine in human neuroblastoma cells. Relationship with alpha-synuclein increase and cell damage
- Author
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Cristina, Gómez-Santos, Marta, Barrachina, Pol, Giménez-Xavier, Esther, Dalfó, Isidre, Ferrer, and Santiago, Ambrosio
- Subjects
Proteomics ,Time Factors ,Dopamine ,Blotting, Western ,Synucleins ,Fluorescent Antibody Technique ,Cell Count ,Nerve Tissue Proteins ,Transfection ,Neuroblastoma ,Cell Line, Tumor ,Humans ,Drug Interactions ,Amines ,Enzyme Inhibitors ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Cell Death ,Dose-Response Relationship, Drug ,CCAAT-Enhancer-Binding Protein-beta ,Carbocyanines ,Gene Expression Regulation, Neoplastic ,CCAAT-Enhancer-Binding Proteins ,alpha-Synuclein ,Benzimidazoles ,Transcription Factor CHOP ,Molecular Chaperones ,Transcription Factors - Abstract
Expression of CCAAT/enhancer-binding protein beta (C/EBP beta) and growth-arrest DNA damage-inducible 153/C/EBP beta homology protein (GADD153/CHOP) increased after incubation of human neuroblastoma SH-SY5Y cells with a range of dopamine concentrations. Dopamine (100 microM) caused an increase in C/EBP beta expression between 2 and 12 h of treatment, with no evident intracellular morphological changes. Dopamine (500 microM) led to the appearance of autophagic-like vacuoles and a marked increase in GADD153/CHOP between 6 and 24 h of treatment. The expression of alpha-synuclein, the main protein of Lewy bodies in Parkinson's disease and other neurological disorders, increased with a profile similar to C/EBP beta. In addition, overexpression of C/EBP beta caused a concomitant increase in the expression of alpha-synuclein but not of GADD153. In contrast, the overexpression of GADD153 did not alter the expression of alpha-synuclein. Inhibition of JNK by SP600125 reduced increases in C/EBP beta and alpha-synuclein expression, whereas inhibition of both JNK and p38MAPK (with SB203580) blocked the increase in GADD153 expression. We conclude that dopamine, through a mechanism driven by stress-activated MAPKs, triggers C/EBP beta and GADD153 expression in a dose-dependent way. Given that the promoter region of the alpha-synuclein gene contains distinct zones that are susceptible to regulation by C/EBP beta, this factor could be involved in the increased expression of alpha-synuclein after dopamine-induced cell stress. GADD153 increase seems to be related with the endoplasmic reticulum stress, autophagy and cell death observed at high dopamine concentrations.
- Published
- 2004