Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis.
Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 micromol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1alpha), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3beta at serine 9 (p-GSK-3beta), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1alpha, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway.
Wu
Xiaomei
X
Department of Neurochemistry, Institute for Nautical Medicine and Jiangsu Key Laboratory of Neuroregeneration, Nantong University, PRC.
Qian
Zhongming
Z
Ke
Ya
Y
Du
Fang
F
Zhu
Li
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004921:Erythropoietin / Q000378:metabolism; D046934:Ginkgolides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology / Q000473:pathology*; D019194:Ischemic Preconditioning; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013997:Time Factors; D051025:bcl-Associated Death Protein / Q000378:metabolism
D046934:Ginkgolides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007783:Lactones; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051025:bcl-Associated Death Protein; D004921:Erythropoietin; C045856:ginkgolide B; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3