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Swainsonine Induces Caprine Luteal Cells Apoptosis via Mitochondrial‐Mediated Caspase‐Dependent Pathway
Author(s) -
Li Wei,
Huang Yong,
Zhao Xiaomin,
Zhang Wenlong,
Dong Feng,
Du Qian,
Tong Dewen
Publication year - 2014
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21585
Subject(s) - apoptosis , cytochrome c , dna fragmentation , microbiology and biotechnology , mitochondrion , caspase , biology , caspase 3 , poly adp ribose polymerase , caspase 9 , caspase 8 , fragmentation (computing) , chemistry , programmed cell death , biochemistry , polymerase , enzyme , ecology
Swainsonine (SW) is an indolizidine alkaloid isolated from a number of poisonous plants. We have previously reported that SW inhibited luteal cell progesterone production by inducing caprine luteal cell apoptosis in vitro; however, the molecular mechanism of this phenomenon remains unclear. In this study, SW‐treated luteal cells showed apoptosis characteristics, including nuclear fragmentation, DNA ladder formation, and phosphatidylserine externalization. Further studies showed that SW activated caspase‐9 and caspase‐3, which subsequently cleaved poly(ADP‐ribose) polymerase. SW also increased in Bax/BcL‐2 ratios, promoted Bax translocation from the cytosol to mitochondria, and triggered the release of cytochrome c from mitochondria into the cytoplasm. However, Fas and Fas ligand induction or caspase‐8 activity did not appear any significant changes. Additional analysis also showed that pan‐caspase inhibitor, caspase‐9 inhibitor, or caspase‐3 inhibitor almost completely protected the cells from SW‐induced apoptosis, but not caspase‐8 inhibitor. Overall, these data demonstrated that SW induced luteal cells apoptosis through a mitochondrial‐mediated caspase‐dependent pathway.