Advanced glycation end products induce apoptosis of human ovarian granulosa COV434 cells and up-regulate pro-inflammatory cytokine HMGB1 autocrine

AIM:To study whether advanced glycation end products (AGEs) induce the apoptosis of human ovarian granulosa COV434 cells, and to explore the possible mechanism. METHODS:Human ovarian granulosa COV434 cells were treated with AGEs at different concentrations. Flow cytometry was used to observe the apoptotic rate. The protein levels of caspase-3 and cleaved caspase-3 were determined by Western blot. The release of high mobility group box 1 protein (HMGB1) in the culture supernatant was measured by ELISA. RESULTS:Compared with control group, early apoptotic rate and late apoptotic rate in 100 mg/L AGEs group and 200 mg/L AGEs group were significantly increased (P<0.05). No obvious difference of caspase-3 protein level in each group was observed, while the protein levels of cleaved caspase-3 in 100 mg/L AGEs group and 200 mg/L AGEs group were significantly increased compared with control group (P<0.05). In addition, compared with control group, pro-inflammatory factor HMGB1 in the culture medium in 100 mg/L AGEs group and 200 mg/L AGEs group was significantly increased. CONCLUSION:The apoptosis of human ovarian granulosa COV434 cells induced by AGEs may be related to pro-inflammatory reaction.