Irisin protects macrophages from oxidized low density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress pathway.

Irisin is a newly discovered myokine which can relieve metabolic disorders and resist atherosclerosis. The effects of irisin on ox-LDL-induced macrophage apoptosis and endoplasmic reticulum stress-related pathways were observed . RAW264.7 macrophages were cultured and pretreated with irisin at 20, 40 and 80 ng/ml for 30 min, followed by culture with 100 mg/L ox-LDL and 5 mg/L tunicamycin (TM) for 12 h. The cell viability and apoptosis were detected by MTT assay and annexin V-FITC double staining. The nuclear translocation of activating transcription factor 6 (ATF6) was detected by immunofluorescence assay. Western blot was used to detect the expressions of p-PERK, p-eIF2α, C/EBP homologous protein (CHOP) and Bcl-2. Irisin reduced lipid accumulation in macrophages in a concentration-dependent pattern and significantly inhibited apoptosis induced by ox-LDL and TM. Compared with ox-LDL and TM groups, the expressions of CHOP, p-PERK and p-eIF2α in the irisin group significantly decreased, the translocation of ATF6 from cytoplasm to nucleus was significantly weakened, and Bcl-2 expression significantly increased. Irisin can alleviate the apoptosis of macrophages induced by ox-LDL, which may be achieved by inhibiting the PERK/eIF2α/CHOP and ATF6/CHOP endoplasmic reticulum stress signaling pathways.