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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.
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页码:87 / 95
页数:9
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