title: Ginkgolide B induces apoptosis via activation of JNK and p21-activated protein kinase 2 in mouse embryonic stem cells.
abstract: Ginkgolide B (GKB), the major active component of Ginkgo biloba extracts, can both stimulate and inhibit apoptotic signaling. We previously showed that ginkgolide treatment of mouse blastocysts induces apoptosis, decreases cell numbers, retards the proliferation and development of mouse embryonic stem cells and blastocysts in vitro, and causes developmental injury in vivo. However, the precise molecular mechanisms underlying its actions are currently unknown. Here, our study further revealed that GKB induced apoptotic biochemical changes, including activation of JNK, caspase-3, and p21-activated protein kinase 2 (PAK2), in ESC-B5 mouse embryonic stem cells. Treatment of ESC-B5 cells with a JNK-specific inhibitor (SP600125) reduced GKB-induced activation of both JNK and caspase-3, indicating that JNK activity is required for GKB-induced caspase activation. Experiments using caspase-3 inhibitors and antisense oligonucleotides against PAK2 showed that caspase-3 activation is required for PAK2 activation and both of these activations are required for GKB-induced apoptosis in ESC-B5 cells.
authors.affiliation: Department of Life Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Yan-Der
authors.initials: YD
authors.lastname: Hsuuw
authors.forename: Tzong-Fu
authors.initials: TF
authors.lastname: Kuo
authors.forename: Kun-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Liu
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lai
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D046934:Ginkgolides / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D014162:Transfection; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000873:Anthracenes; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D046934:Ginkgolides; D007783:Lactones; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C432165:pyrazolanthrone; C045856:ginkgolide B; C515909:Pak2 protein, mouse; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3