Abstract
To explore the ischemic tolerance induced by Ginkgolides in PC12 cells and its possible molecular mechanism. An ischemic model was developed in PC12 cell line with deprivation of oxygen-glucose (OGD). PC12 cells was randomly divided into four groups: 9 hours ischemia group, 1.5 hours ischemic preconditioning + 9 hours ischemia group, Ginkgolides preconditioning + 9 hours ischemia group and control group. Cells viability was examined by MTT assay and cellular morphology was analyzed under the phase-contrast microscope. The molecular mechanism of Ginkgolides induced ischemic tolerance was pinpointedby analyzing the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO). The DNA binding activities of HIF-1 in PC12 cells were examined by electrophoretic mobility shift assay. In ischemic model, the viability of PC12 cells was decreased (49.3 +/- 2.8)% after OGD for 9 hours. However, Ginkgolides pretreatment could remarkably increase the viability of PC12 cells (65.9 +/- 2.8)% (P < 0.01). Pretreatment of Ginkgolides for 24 hours could largely rescue the morphology of PC12 cells to the damage of subsequent exposure to 9 hours ischemia insult, many cellular bodies were intact and many neurites and network of PC12 cells were still exist. At molecular level, the expression of HIF-1alpha was greatly induced by Ginkgolides treatment after compared with the control group (P < 0.01). The DNA binding activities of HIF-1 in PC12 cells pretreated with Ginkgolides was also increased. And it activates its downstream target EPO, the protein expression (P < 0.01). The pretreatment of Ginkgolides could induce tolerance against ischemia in PC12 cells. The molecular mechanism of this process may involve in the activation of HIF-1alpha and the DNA binding activity of HIF-1 and its downstream target EPO.
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