title: PI3K p55γ promoter activity enhancement is involved in the anti-apoptotic effect of berberine against cerebral ischemia-reperfusion.
abstract: Berberine is a candidate clinical neuroprotective agent against ischemic stroke. In the present study, we examined the influence of the PI3K/Akt pathway in mediating the anti-apoptotic effects of berberine. Oxygen-glucose deprivation and reoxygenation of nerve growth factor-differentiated PC12 cells and primary neurons, and bilateral common carotid artery occlusion in mice were used as in vitro and in vivo ischemia models. We found that the anti-apoptotic effects of berberine against ischemia were indeed mediated by the increased phosphor-activation of Akt (higher p-Akt to total Akt), leading to the intensified phosphorylation of Bad and the decreased cleavage of the pro-apoptotic protease caspase-3. Berberine action is specific for PI3K, rather than the upstream receptor tyrosine kinase. The anti-apoptotic effect is maintained in the presence of tyrosine kinase inhibitor genistein and the epidermal growth factor receptor inhibitor PD153035, but is suppressed by the PI3K inhibitor Ly294002 and the Akt inhibitor Akti-1/2.The unique PI3K regulatory subunit p55γ was upregulated by berberine during ischemia-reperfusion and was not blocked by these inhibitors. We constructed a reporter plasmid to detect PI3K p55γ promoter activity and found that berberine enhanced PI3K p55γ promoter activity during cerebral ischemia-reperfusion.
authors: Protein Science Laboratory of the Ministry of Education, Laboratory of Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Jun
authors: J
authors: Hu
authors: Yushuang
authors: Y
authors: Chai
authors: Yugang
authors: Y
authors: Wang
authors: Michael M
authors: MM
authors: Kheir
authors: Huiying
authors: H
authors: Li
authors: Zhiyi
authors: Z
authors: Yuan
authors: Hongjiao
authors: H
authors: Wan
authors: Dongming
authors: D
authors: Xing
authors: Fan
authors: F
authors: Lei
authors: Lijun
authors: L
authors: Du
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications*; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D051379:Mice; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001599:Berberine; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3