Bcl—2-Bax-福建医科大学英文版.pdf

Arch Toxicol DOI 10.1007/s00204-011-0745-7 MOLECULAR TOXICOLOGY 2,5-Hexanedione induces human ovarian granulosa cell apoptosis through BCL-2, BAX, and CASPASE-3 signaling pathways Yan Sun · Yuan Lin · Hong Li · Jin Liu · Xiaohua Sheng · Wenchang Zhang Received: 30 June 2011 / Accepted: 11 August 2011 © Springer-Verlag 2011 Abstract Studies have shown that 2,5-hexanedione (2,5- decreased. However, a marked dose-dependent increase in HD) is the main active metabolite of n-hexane in the human the expression of BAX and active CASPASE-3 (p17) was body. The toxicity of n-hexane and 2,5-hexanedione has observed in human ovarian granulosa cells. These results been extensively researched, but toxicity to the reproduc- suggest that the mechanisms of 2,5-HD causing increased tive system, especially the impact on female reproductive apoptosis in human ovarian granulosa cells might be function, has been less frequently reported. In this study, through BCL-2, BAX, and CASPASE-3 signaling path- we exposed human ovarian granulosa cells to 0, 16, 64, and ways. 256 M 2,5-HD in vitro for 24 h. Through hematoxylin– eosin (HE) staining, Hoechst 33342 staining, transmission Keywords 2,5-Hexanedione · Granulosa cells · Ovarian · electron microscopy, and Xow cytometry using FITC- Apoptosis · BCL-2 · BAX · CASPASE-3 Annexin V/PI double staining, 2,5-HD was demonstrated to cause signiWcant apoptosis of human ovarian granulosa cells in a dose-dependent manner. As part of our continuing Introduction studies, we investigated the underlying apoptosis mecha- nism of human ovarian granulosa cells exposed to 0, 16, 64, n-Hexane is widely used as an organic solvent in adhesive and 256 M 2,5-H