Tribble 3, a novel oxidized low-density lipoprotein-inducible gene, is induced via the activating transcription factor 4-C/EBP homologous protein pathway.
Clin Exp Pharmacol Physiol
; 37(1): 51-5, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19566842
ABSTRACT
1. C/EBP homologueueueous protein (CHOP), an endoplasmic reticulum (ER) stress-inducible protein, has a critical role in regulation of the cell cycle and apoptosis by forming heterodimers with other C/EBP proteins. However, how CHOP function is regulated remains to be determined. The human homologue of Drosophila tribbles (TRIB3) is associated with CHOP and is upregulated by oxidized low-density lipoprotein (ox-LDL). The aim of the present study was to investigate the role of CHOP in ox-LDL-induced TRIB3 expression in macrophages. 2. Human monocyte-derived macrophages were treated with various concentrations of ox-LDL (0, 2.5, 5, 10, 25 and 50 microg/mL) or 2 microg/mL tunicamycin for 0, 4, 8, 16, 24 and 48 h or were transfected with CHOP or TRIB3 expression plasmid and TRIB3 targeting short interference RNA (siRNA). The expression of CHOP and activating transcription factor 4 (ATF4) mRNA in treated cells was detected by quantitative real-time polymerase chain reaction (PCR). 3. The expression of CHOP and ATF4 mRNA increased with increasing concentrations of ox-LDL and duration of time. The ox-LDL-induced expression of TRIB3 mRNA was upregulated later than the expression of CHOP and ATF4 mRNA. Overexpression of CHOP increased the mRNA expression of TRIB3, which was further increased in CHOP-overexpressing macrophages treated with ox-LDL. Overexpression of TRIB3 suppressed the expression of CHOP, whereas TRIB3 silencing increased CHOP expression following ox-LDL stimulation by a negative feedback mechanism. 4. In conclusion, the expression of ATF4 and CHOP is upregulated by ox-LDL in a dose- and time-dependent manner in naturally differentiated human macrophages. Oxidized LDL induces TRIB3 expression via an ATF4/CHOP-dependent ER stress pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Transdução de Sinais
/
Regulação para Cima
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Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Fator 4 Ativador da Transcrição
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Fator de Transcrição CHOP
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Lipoproteínas LDL
Limite:
Humans
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China