title: Carnosic acid attenuates apoptosis induced by amyloid-β 1-42 or 1-43 in SH-SY5Y human neuroblastoma cells.
abstract: Amyloid-beta (Aβ) peptides, Aβ 1-42 (Aβ42) and Aβ43 in particular, cause neurotoxicity and cell death in the brain of Alzheimer's disease (AD) at higher concentrations. Carnosic acid (CA), a phenolic diterpene compound in the labiate herbs rosemary and sage, serves as an activator for neuroprotective and neurotrophic functions in brain cells. We investigated the effect of CA on apoptosis induced by Aβ42 or Aβ43 in cultured SH-SY5Y human neuroblastoma cells. Treatment of the cells with Aβ42 or Aβ43 (monomer, 10 μM each) induced apoptosis, which was confirmed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF). Concurrently, the Aβ treatment induced the activation of caspase (Casp) cascades including an effector Casp (Casp3) and initiator Casps (Casp4, Casp8 and Casp9). Pretreatment of the cells with CA (10 μM) partially attenuated the apoptosis induced by Aβ42 or Aβ43. CA pretreatment also reduced the cellular oligomers of Aβ42 and Aβ43. These results suggest that CA suppressed the activation of Casp cascades by reducing the intracellular oligomerization of exogenous Aβ42/43 monomer. The ingestion of an adequate amount of CA may have a potential in the prevention of Aβ-mediated diseases, particularly AD.
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Meng
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: hidemi_yoshida@gakushikai.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Hirosaki University School of Medicine and Hospital, Hirosaki 036-8563, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.affiliation: Department of Pediatrics, Hirosaki University School of Medicine and Hospital, Hirosaki 036-8563, Japan; Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki 036-8560, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Junsei
authors.initials: J
authors.lastname: Mimura
authors.affiliation: Research and Development Center, Nagase & Co. Ltd., 2-2-3, Kobe 651-2241, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Kosaka
authors.affiliation: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kawaguchi
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D010936:Plant Extracts; C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43); D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C018381:salvin
keywords: Alzheimer's disease; Aβ42; Aβ43; Carnosic acid; Caspases; SH-SY5Y