Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages / 生理学报
Acta Physiologica Sinica
;
(6): 612-618, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-255995
ABSTRACT
The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 μmol/L thapsigagin (TG) for 4 h. In addition, RAW264.7 cells were incubated with 0.5, 1 and 2 mg/L TM for 4 h or treated with 2 mg/L TM for 1, 2 and 4 h, respectively. The intracellular total cholesterol (TC) content was measured using a tissue/cell total cholesterol assay kit. The protein and mRNA expressions of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot and real-time PCR, respectively. Dil-ox-LDL uptake was detected using a microplate reader. The results showed that ox-LDL-induced cholesterol accumulation in macrophages was attenuated by PBA, an ERS inhibitor. Ox-LDL caused significant SR-A1 upregulation with concomitant activation of ERS as assessed by upregulation of GRP78, whereas PBA significantly inhibited the ox-LDL-induced SR-A1 upregulation (P < 0.05) and slightly decreased GRP78 expression by 39.3% (P = 0.057). TM, an ERS inducer, upregulated SR-A1 protein expression and ox-LDL uptake in dose- and time-dependent manner, but had no significant effect on SR-A1 mRNA level. However, the TM- or TG-induced SR-A1 upregulation and ox-LDL uptake were significantly mitigated by PBA. These data indicate that ERS plays a critical role in ox-LDL-induced SR-A1 upregulation, which in turn enhances the foam cell formation by uptaking more ox-LDL.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Regulação para Cima
/
Linhagem Celular
/
Colesterol
/
Receptores Depuradores Classe A
/
Estresse do Retículo Endoplasmático
/
Proteínas de Choque Térmico
/
Lipoproteínas LDL
/
Macrófagos
/
Metabolismo
Limite:
Animais
Idioma:
Chinês
Revista:
Acta Physiologica Sinica
Ano de publicação:
2014
Tipo de documento:
Artigo
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