title: Suppressive effect of nobiletin, a citrus polymethoxyflavonoid that downregulates thioredoxin-interacting protein expression, on tunicamycin-induced apoptosis in SK-N-SH human neuroblastoma cells.
abstract: Increased expression of thioredoxin-interacting protein (TXNIP) has recently been proved to be a crucial event for irremediable endoplasmic reticulum (ER) stress resulting in the programmed cell death (apoptosis) of pancreatic β-cells. The present study demonstrated that treatment with 1-10 μg/ml tunicamycin, a potent revulsant of ER stress, drastically induced TXNIP expression accompanied by the generation of cleaved caspase-3 as an indicator of apoptosis in SK-N-SH human neuroblastoma cells. This result substantiated that TXNIP is also involved in neurodegeneration triggered by ER stress. Moreover, we evaluated the effects of nobiletin, a citrus polymethoxyflavonoid, on tunicamycin-induced apoptosis and TXNIP expression in SK-N-SH cells, because we reported previously that this flavonoid might be able to reduce TXNIP expression. Co-treatment of SK-N-SH cells with 100 μM nobiletin and 1 μg/ml tunicamycin for 24h strongly suppressed apoptosis and increased TXNIP expression induced by 1 μg/ml tunicamycin treatment alone. In addition, we proved that the ability of 100 μM nobiletin treatment to reduce TXNIP expression is exerted from 3h after the onset of treatment. Therefore, the protective and ameliorative effects of nobiletin on neuronal degeneration and impaired memory, which several studies using animal models have demonstrated, might arise in part from nobiletin's ability to repress TXNIP expression.
authors.affiliation: Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ikeda
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Nemoto
authors.forename: Chiaki
authors.initials: C
authors.lastname: Yoshida
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.forename: Junki
authors.initials: J
authors.lastname: Mori
authors.forename: Saori
authors.initials: S
authors.lastname: Soejima
authors.forename: Akihito
authors.initials: A
authors.lastname: Yokosuka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mimaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohizumi
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D047309:Flavones; D014415:Tunicamycin; D013879:Thioredoxins; C008661:nobiletin
keywords: Apoptosis; Endoplasmic reticulum stress; Neuroblastoma; Neuroprotection; Nobiletin; TXNIP