Inhibitory effect of caveolin-1 on endoplasmic reticulum stress-induced apoptosis in macrophages via p38 MAPK pathway.
- Author:
Wen YUE
1
;
Shu-Tong YAO
;
Xiao ZHOU
;
Yan-Hong SI
;
Hui SANG
;
Jia-Fu WANG
;
Zhan-Ping SHANG
Author Information
1. Pathophysiology Department, Taishan Medical College, Taian, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
drug effects;
Caveolin 1;
genetics;
metabolism;
Cell Line;
Endoplasmic Reticulum Stress;
physiology;
Filipin;
pharmacology;
MAP Kinase Signaling System;
Macrophages;
cytology;
drug effects;
Mice;
Thapsigargin;
pharmacology;
Transcription Factor CHOP;
metabolism;
p38 Mitogen-Activated Protein Kinases;
metabolism
- From:
Acta Physiologica Sinica
2012;64(2):149-154
- CountryChina
- Language:Chinese
-
Abstract:
Endoplasmic reticulum (ER) stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. The purpose of the present study was to investigate the effects of caveolin-1 (Cav-1) on ER stress-induced apoptosis in cultured macrophages and the underlying mechanisms. RAW264.7 cells were incubated with thapsigargin (TG) to establish ER stress model. And Cav-1 expression was detected by Western blot. After being pretreated with filipin(III), a caveolae inhibitor, RAW264.7 cells were assayed with flow cytometry and confocal laser scanning microscopy to detect cell apoptosis. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation and C/EBP homologous protein (CHOP) expression were detected with Western blot. The results showed that Cav-1 expression was markedly increased at early stage of TG treatment (P < 0.05) and then decreased with prolonged or high dose TG treatments. The increasing of Cav-1 expression induced by TG in RAW264.7 cells was abolished under inhibition of caveolae by filipin(III) (P < 0.05). The effect of TG on apoptosis of RAW264.7 cells was further augmented after pretreatment with filipin(III) (P < 0.05). Western blotting showed that MAPK phosphorylation induced by TG was inhibited by filipin(III) in RAW264.7 cells (P < 0.05), whereas CHOP remained unchanged (P > 0.05). These results suggest that Cav-1 may play a critical role in suppressing ER stress-induced macrophages apoptosis in vitro, and one of the mechanisms may be correlated with the activation of p38 MAPK prosurvival pathway.
