PQS attenuates cardiomyocyte apoptosis induced by thapsigargin through inhibiting endoplasmic reticulum stress / 中国病理生理杂志

ABSTRACT

AIM:To study the effect of Panax quinquefolium saponin (PQS) on cardiomyocyte apoptosis in-duced by thapsigargin ( TG) .METHODS:Primary cultured cardiomyocytes from neonatal SD rats were divided into con-trol group, TG group, PQS (40 mg/L, 80 mg/L and 160 mg/L) +TG group, si-PERK+TG group, and mock+TG group.The cells were treated with 1 μmol/L TG for 24 h to induce apoptosis.The PERK gene in the cardiomyocytes was knocked down by RNAi.The cell viability was detected by CCK-8 assay.Apoptosis was analyzed by flow cytometry.Wes-tern blotting was used to determine the expression of ERS molecules GRP78, CRT, ATF4 and CHOP, anti-apoptosis pro-tein Bcl-2 and pro-apoptosis protein Bax.RESULTS: Compared with control group, TG significantly and the apoptosis, reduced the cell viability (P<0.05), increased the phosphorylation of PERK and eIF2α, increased the expression of GRP78, CRT, ATF4, CHOP and pro-apoptosis protein Bax, and decreased the expression of anti-apoptosis protein Bcl-2 (P<0.05).Compared with TG group, PQS treatment (160 mg/L) significantly reduced the apoptosis and increased the cell viability (P<0.05).All the 3 different concentrations of PQS significantly increased the expression of anti-apoptosis protein Bcl-2 and reduced the expression of pro-apoptosis protein Bax (P<0.05) in a dose-dependent manner.PQS pre-treatment and knockdown of PERK both reduced the protein levels of GRP78, CRT, PERK, p-PERK, eIF2α, p-eIF2α, ATF4, CHOP and pro-apoptosis protein Bax, and increased the expression of anti-apoptosis protein Bcl-2 (P<0.05). CONCLUSION:PQS at concentration of 160 mg/L attenuated cardiomyocyte apoptosis induced by TG.PQS had the simi-lar effect as PERK knockdown on cardiomyocyte apoptosis.The mechanism may be associated with inhibiting PERK-eIF2α-ATF4-CHOP pathway of ERS-related apoptosis.