title: Cell-type-specific regulation of raft-associated Akt signaling.
abstract: 20S-protopanaxadiol (aPPD) is a metabolite of ginseng saponins, which is reported to be pro-apoptotic in some cells but anti-apoptotic in neuronal cells by regulating Akt signaling. Owing to its cholesterol-like structure, we hypothesized that aPPD may regulate Akt signaling by interacting with lipid rafts. Here, we compared Akt signaling in glioblastoma U87MG and neuroblastoma Neuro-2a cells treated with aPPD. aPPD did not change Akt activity in the total plasma membranes of each cell type, but drastically altered the activity of raft-associated Akt. Strikingly, Akt activity was decreased in the rafts of U87MG cells but increased in N2a cells by aPPD through regulating raft-associated dephosphorylation. The bidirectional regulation of raft-associated Akt signaling by aPPD enhanced the chemotoxicity of Paclitaxel or Vinblastine in U87MG cells but attenuated the excitotoxicity of N-methyl-D-aspartate in N2a cells. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of cells, which allows for the possibility of cell-type-specific targeting for which aPPD might prove to be a useful agent.
authors.affiliation: Department of Pathology, School of Preclinical Medicine, Beijing University of Chinese Medicine, Chaoyang District, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Yang
authors.forename: X
authors.initials: X
authors.lastname: Bu
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Jia
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012502:Sapogenins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity
chemical_list: D010936:Plant Extracts; D012502:Sapogenins; D051057:Proto-Oncogene Proteins c-akt; C062916:protopanaxadiol