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[Inhibitory effect of caveolin-1 on endoplasmic reticulum stress-induced apoptosis in macrophages via p38 MAPK pathway.] [Article in Chinese]

YUE Wen, YAO Shu-Tong, ZHOU Xiao, SI Yan-Hong, SANG Hui, WANG Jia-Fu, SHANG Zhan-Ping^*

Pathophysiology Department, Taishan Medical College, Taian 271000, China； Pathophysiology Department, Shandong Medical College, Linyi 276002, China

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.

Key words: caveolin-1; endoplasmic reticulum stress; p38 MAPK; CHOP; apoptosis; Macrophage

Received: 2011-09-23　　Accepted: 2011-12-27

Corresponding author: 商战平　　E-mail: zhpshang@tsmc.edu.cn

Citing This Article：

YUE Wen, YAO Shu-Tong, ZHOU Xiao, SI Yan-Hong, SANG Hui, WANG Jia-Fu, SHANG Zhan-Ping. [Inhibitory effect of caveolin-1 on endoplasmic reticulum stress-induced apoptosis in macrophages via p38 MAPK pathway.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (2): 149-154 (in Chinese with English abstract).