title: Swainsonine induces caprine luteal cells apoptosis via mitochondrial-mediated caspase-dependent pathway.
abstract: 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.
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.
authors: Wei
authors: W
authors: Li
authors: Yong
authors: Y
authors: Huang
authors: Xiaomin
authors: X
authors: Zhao
authors: Wenlong
authors: W
authors: Zhang
authors: Feng
authors: F
authors: Dong
authors: Qian
authors: Q
authors: Du
authors: Dewen
authors: D
authors: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006041:Goats / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017026:Swainsonine / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D017026:Swainsonine
keywords: Apoptosis; Caspase; Luteal Cell; Mitochondrial Pathway; Swainsonine