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Title: Ginkgolides protect PC12 cells against hypoxia-induced injury by p42/p44 MAPK pathway-dependent upregulation of HIF-1α expression and HIF-1DNA-binding activity
Authors: Zhu, L
Ke, Y
Wu, X
Yang, L
Qian, ZM
Issue Date: 2008
Source: Journal of cellular biochemistry, 2008, v. 103, no. 2, p. 564-575
Abstract: We hypothesized that the neuroprotective role of the standardized Ginkgo biloba (Ginkgoaceae) extract EGb 761 under hypoxic conditions might be associated with its function to increase HIF-1 activity based on the fact that oxygen availability is crucial for cellular metabolism and viability and that HIF-1 plays an essential role in cellular oxygen homeostasis under hypoxic conditions. In this study, we therefore investigated the effects of ginkgolides, the main constituent of the non-flavone fraction of EGb 761, on the content and activity of HIF-1α, a key factor to determine HIF-1 activity, in hypoxic PC12 cells induced by cobalt chloride. Our data demonstrated that ginkgolides have a significant protective role against hypoxia-induced injury in the PC12 cells. The findings also strongly support our hypothesis that the protective role of ginkgolides is due to the up-regulation of HIF-1α protein expression and modification through the ginkgolides-induced activation of the p42/p44 MAPK pathway. In addition, it was evident that ginkgolides could significantly increase the HIF-1 DNA binding activity, which might also be associated with the protective effects of ginkgolides by promoting the expression of target genes of HIF-1 under hypoxic conditions.
Keywords: Neuroprotection
Extracellular signal-regulated kinase (ERK)
HIF-1α expression and modification
activation of p42/p44 (ERK) MAPK pathway
Publisher: John Wiley & Sons
Journal: Journal of cellular biochemistry 
ISSN: 0730-2312 (print)
1097-4644 (online)
DOI: 10.1002/jcb.21427
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