title: Carnosic acid protects starvation-induced SH-SY5Y cell death through Erk1/2 and Akt pathways, autophagy, and FoxO3a.
abstract: Carnosic acid (CA) is recognized as a unique neuroprotective compound in the herb rosemary, since it induces expression of antioxidant enzymes including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), and glutathione S-transferase (GST) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a nuclear transcription factor. In this study, we examined the cytoprotective effects of CA against starvation. We found that CA protected starvation-induced SH-SY5Y cell death by activating Akt and extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, CA induced moderate autophagy and dephosphorylation of a transcriptional factor, the forkhead box protein O3a (FoxO3a). These effects of CA play an important role in cytoprotection.
authors.affiliation: a Department of Human Life Science Education, Graduate School of Education , Hiroshima University , Hiroshima , Japan ;
authors.forename: Sachi
authors.initials: S
authors.lastname: Shibata
authors.affiliation: b Department of Regenerative Medicine , Medical Center for Translational and Clinical Research, Hiroshima University Hospital , Hiroshima , Japan ;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishitobi
authors.affiliation: b Department of Regenerative Medicine , Medical Center for Translational and Clinical Research, Hiroshima University Hospital , Hiroshima , Japan ;
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyaki
authors.affiliation: c Kawaoka Clinic , Hiroshima , Japan ;
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawaoka
authors.affiliation: d Faculty of Education , Saga University , Saga , Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kayashima
authors.affiliation: a Department of Human Life Science Education, Graduate School of Education , Hiroshima University , Hiroshima , Japan ;
authors.forename: Kiminori
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D027542:Rosmarinus / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D045784:Abietanes; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; C018381:salvin
keywords: Autophagy; FoxO3a; SH-SY5Y cells; carnosic acid; starvation