title: [Inhibitory effect of quercetin preconditioning on tunicamycin-induced apoptosis in macrophages and its mechanism].
abstract: The purposes of the present study were to investigate the inhibitory effect of quercetin (QUE) preconditioning on endoplasmic reticulum stress (ERS) inducer tunicamycin (TM)-induced apoptosis in RAW264.7 macrophages and the underlying molecular mechanisms. RAW264.7 cells were pretreated with different concentrations (20, 40, and 80 μmol/L) of QUE for 30 min and then treated with TM (5 mg/L) for 12 h. Cell viability and apoptosis were determined using MTT assay and Annexin V-FITC apoptosis detection kit, respectively. The nuclear translocation of activating transcription factor 6 (ATF6) in cells was detected by immunofluorescence analysis and Western blot. Protein and mRNA expressions of C/EBP homologous protein (CHOP) and Bcl-2 were examined by Western blot and real-time PCR, respectively. The results showed that TM reduced cell viability and induced apoptosis in RAW264.7 macrophages. The cytotoxic effects of TM were significantly inhibited by QUE pretreatment at the concentrations of 40 and 80 μmol/L. Interestingly, we found that QUE also significantly suppressed the TM-induced translocation of ATF6, an ERS sensor, from the cytoplasm to the nucleus. In addition, exposure of RAW264.7 macrophages to TM resulted in a significant increase of the expression of CHOP, a transcription factor regulated by ATF6 under conditions of ERS, as well as a decrease of Bcl-2 at transcript and protein levels. QUE blocked these effects in a dose-dependent manner. These data indicate that QUE can protect RAW264.7 cells from TM-induced apoptosis and that the mechanism at least partially involves its ability to inhibit the ATF6-CHOP signaling pathway.
authors: Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong, China.
authors: Shu-Tong
authors: ST
authors: Yao
authors: Cheng
authors: C
authors: Miao
authors: Qing-Hua
authors: QH
authors: Liu
authors: Yan-Yan
authors: YY
authors: Li
authors: Hua
authors: H
authors: Tian
authors: Yun-Yun
authors: YY
authors: Wang
authors: Bian-Ying
authors: BY
authors: Ma
authors: Yong-Qi
authors: YQ
authors: Fang
authors: Shu-Cun
authors: SC
authors: Qin
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D011794:Quercetin