Induction of C/EBPP and GADD153 expression by dopamine in human neuroblastoma cells relationship with α-synuclein increase and cell damage

被引:42
作者
Gómez-Santos, C
Barrachina, M
Giménez-Xavier, P
Dalfó, E
Ferrer, I
Ambrosio, S
机构
[1] Univ Barcelona, IDIBELL, Unitat Bioquim, Dept Ciencias Fisiol 2, E-08907 Barcelona, Spain
[2] Ctr Nacl Invest Enfermedades Neurol, Barcelona, Spain
[3] Univ Barcelona, Dept Biol Cellular & Anat Patol, Barcelona, Spain
[4] Bellvitge Hosp, IDIBELL, Inst Neuropathol, Barcelona, Spain
关键词
dopamine toxicity; SH-SY5Y cells; alpha-synuclein; C/EBP beta; GADD153/CHOP;
D O I
10.1016/j.brainresbull.2004.11.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Expression of CCAAT/enhancer-binding protein beta (C/EBPbeta) and growth-arrest DNA damage-inducible t53/C/EBPbeta homology protein (GADD153/CHOP) increased after incubation of human neuroblastoma SH-SY5Y cells with a range of dopamine concentrations. Dopamine (100 muM) caused an increase in C/EBPbeta expression between 2 and 12 h of treatment, with no evident intracellular morphological changes. Dopamine (500 muM) 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 a-synuclein, the main protein of Lewy bodies in Parkinson's disease and other neurological disorders, increased with a profile similar to C/EBPbeta. In addition, overexpression of C/EBPbeta 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/EBPbeta 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/EBPbeta 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/EBPbeta, this factor could be involved in the increased expression of a-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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:87 / 95
页数:9
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