Gingko biloba extract (EGb 761) prevents cerebral ischemia-induced p70S6 kinase and S6 phosphorylation.
EGb 761 is an extract of Gingko biloba that exhibits neuroprotective effects against cerebral ischemia. The mammalian target of rapamycin (mTOR) is a critical downstream effector of Akt and a central regulator of ribosomal biogenesis and protein synthesis. We investigated whether EGb 761 regulates Akt downstream targets, including mTOR, p70S6 kinase, and S6 phosphorylation. Adult male rats were treated with vehicle or EGb 761 (100 mg/kg) prior to middle cerebral artery occlusion (MCAO). Brains were collected at 24 hours after MCAO and the cerebral cortex regions were examined. We previously showed that EGb 761 significantly reduces infarct volume and decreases the number of TUNEL-positive cells in the cerebral cortex. Ischemic brain injury induces a decrease in Akt up-stream target, PDK1 phosphorylation. The levels of phospho-mTOR, phospho-p70S6 kinase, and phospho-S6 are subsequently decreased in regions affected by ischemic injury. However, EGb 761 prevented injury-induced decreases in these protein levels. We confirmed that EGb 761 inhibits injury-induced decreases in the number of positive cells for phospho-p70S6 kinase and phospho-S6. The results of this study provide evidence that EGb 761 protects neuronal cells against ischemic brain injury by preventing injury-induced decreases in p70S6 kinase and S6 phosphorylation.
Koh
Phil-Ok
PO
Department of Anatomy, Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea. pokoh@gsnu.ac.kr
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism / Q000517:prevention & control*; D020441:Ginkgo biloba; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000096983:Ginkgo Extract
D018696:Neuroprotective Agents; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D012269:Ribosomal Proteins; D058570:TOR Serine-Threonine Kinases; C000631434:Pdk1 protein, rat; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract