title: Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression of RTP801.
abstract: RTP801 (also known as REDD1), a stress-related protein, is induced by several environmental stresses such as ischemia and cigarette smoke. Although ischemia can dramatically up-regulate RTP801 expression in brain ischemia, up to now, the exact relation between RTP801 and neuronal death in ischemia is poorly understood. In the current study, using oxygen and glucose deprivation as an in vitro ischemic model in primary cultured cortical neurons, we found that the expression of RTP801 increased progressively with prolongation of ischemic duration, in which the expression of RTP801 is positively correlated with the release of lactate dehydrogenase (LDH) in neurons, and knockdown of RTP801 promoted neuronal survival in ischemia-reperfusion. It was further found that ginkgolide B (GB) could significantly increase cell viability and decrease LDH release, and at the same time reduce the levels of RTP801 mRNA and protein in neurons after ischemia and reperfusion. Moreover, GB-induced reduction in expression of RTP801 was blocked by application of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that RTP801 could play a detrimental role on neurons in ischemia, and GB might protect neurons against ischemic injury by inhibiting RTP801 expression via PI3K pathway.
authors: Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China.
authors: Xiaomei
authors: X
authors: Wu
authors: Medical Laboratory Center, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China.
authors: Jianyou
authors: J
authors: Su
authors: Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China.
authors: Lei
authors: L
authors: Chen
authors: Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China.
authors: Baodong
authors: B
authors: Ma
authors: Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China.
authors: Xiaosu
authors: X
authors: Gu
authors: Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China. zhuli65@163.com.
authors: Li
authors: L
authors: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D046934:Ginkgolides / Q000494:pharmacology / Q000627:therapeutic use*; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C450979:Ddit4l protein, mouse; D046934:Ginkgolides; D007783:Lactones; D018696:Neuroprotective Agents; D010936:Plant Extracts; D014157:Transcription Factors; C045856:ginkgolide B
keywords: Ginkgolide B; Ischemia; Ischemia–Reperfusion; Neuron; Phosphatidylinositol 3-kinase; RTP801