title: An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease.
abstract: Various types of stress, such as disruption of calcium homeostasis, inhibition of protein glycosylation and reduction of disulfide bonds, result in accumulation of misfolded proteins in the endoplasmic reticulum (ER). The initial cellular response involves removal of such proteins by the ER, but excessive and/or long-term stress results in apoptosis. In this study, we used a randomized ribozyme library and ER stress-mediated apoptosis (tunicamycin-induced apoptosis) in SK-N-SH human neuroblastoma cells as a selective phenotype to identify factors involved in this process. We identified a double-stranded RNA-dependent protein kinase (PKR) as one of the participants in this process. The level of nuclear PKR was elevated, but the level of cytoplasmic PKR barely changed in tunicamycin-treated SK-N-SH cells. Furthermore, tunicamycin also raised levels of phosphorylated PKR in the nucleus. We also detected the accumulation of phosphorylated PKR in the nuclei of autopsied brain tissues in Alzheimer's disease. Thus, PKR might play a role in ER stress-induced apoptosis and in Alzheimer's disease.
authors.affiliation: Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba Science City, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Onuki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Bando
authors.forename: Eigo
authors.initials: E
authors.lastname: Suyama
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Baba
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D016337:RNA, Catalytic / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D016337:RNA, Catalytic; D014415:Tunicamycin; D019892:eIF-2 Kinase