Ginkgolides mimic the results of hypoxic preconditioning to guard C6 cells towards ischemic damage.
PMID:
Int J Biochem Cell Biol. 2008 ;40(4):651-62. Epub 2007 Oct 22. PMID: 18054269
Summary Title:
Ginkgolides mimic the results of hypoxic preconditioning to guard C6 cells towards ischemic damage by up-regulation of hypoxia-inducible factor-1 alpha and erythropoietin.
Summary:
Hypoxic preconditioning can play a big neuroprotective function. Nevertheless, it has not been employed clinically due to security considerations. To discover a safer preconditioning stimulus that’s each sensible and efficient, we investigated whether or not ginkgolides are able to preconditioning as hypoxia to guard C6 cells towards ischemic damage. We demonstrated that each ginkgolides (37.5microg/mL) and hypoxia (1% O(2) for 16h) can considerably enhance cell viabilities and expression of phosphorylated glycogen synthase kinase (p-GSK), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) in ischemic cells. The inhibitors of mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3′-kinase (PI3K) considerably however not utterly lowered the improved expression of those proteins and cell viabilities induced by ginkgolides and hypoxic preconditioning. These indicated that ginkgolides may mimic hypoxic preconditioning by growing expression of HIF-1alpha in addition to its goal protein EPO and that the ginkgolides and hypoxic preconditioning function may be partly mediated by the activation of the p42/p44-mitogen-activated protein kinase and phosphatidylinositol 3′-kinase/AKT/glycogen synthase kinase 3beta pathways. The same tendency within the adjustments of protein expression, cell viabilities and responses to MAPK or PI3K inhibitors of the cells handled with ginkgolides and hypoxia means that ginkgolides and hypoxic preconditioning may function by related mechanisms. The findings additionally suggest that ginkgolides may need the potential for medical use to stop damage in high-risk circumstances.
