title: [Inhibitory effect of caveolin-1 on endoplasmic reticulum stress-induced apoptosis in macrophages via p38 MAPK pathway].
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.
authors.affiliation: Pathophysiology Department, Taishan Medical College, Taian, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.forename: Shu-Tong
authors.initials: ST
authors.lastname: Yao
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Si
authors.forename: Hui
authors.initials: H
authors.lastname: Sang
authors.forename: Jia-Fu
authors.initials: JF
authors.lastname: Wang
authors.forename: Zhan-Ping
authors.initials: ZP
authors.lastname: Shang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005372:Filipin / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; C497251:Ddit3 protein, rat; D051742:Transcription Factor CHOP; D019284:Thapsigargin; D005372:Filipin; D048051:p38 Mitogen-Activated Protein Kinases