Up-regulation of HIF-1alpha expression induced by ginkgolides in hypoxic neurons.
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular and systemic oxygen homeostasis. Recently, we demonstrated that ginkgolides, the main constituents of the non-flavone fraction of the standardized Ginkgo biloba (Ginkgoaceae) extract EGb 761, have a significant protective role against chemical and physical hypoxia-induced injury in neurons and PC12 cells. Based on the findings and the function of HIF-1 as a master regulator of oxygen homeostasis, we speculate that the protective role of ginkgolides might be mediated by HIF-1. In this study, we therefore investigated the effects of ginkgolides on the expression of HIF-1alpha, the cell viability and the lactate dehydrogenase (LDH) release in the hypoxic cortical neuron. We demonstrated that ginkgolides significantly increase the expression of HIF-1alpha and the cell viability as well as decrease the release of LDH in the hypoxic neuron. The findings suggested that the neuroprotective role of ginkgolides against hypoxia-induced injury might be associated with its role to up-regulate the expression of HIF-1alpha in the hypoxic neurons.
Zhu
Li
L
Institute for Nautical Medicine and Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PRC. zhulili65@yahoo.com
Wu
Xiao-Mei
XM
Yang
Lei
L
Du
Fang
F
Qian
Zhong Ming
ZM
D000818:Animals; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D046934:Ginkgolides / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation
D046934:Ginkgolides; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase