title: NGF-induced phosphatidylinositol 3-kinase signaling pathway prevents thapsigargin-triggered ER stress-mediated apoptosis in PC12 cells.
abstract: Tunicamycin, an inhibitor of the glycosylation of newly biosynthesized proteins, induces endoplasmic reticulum (ER) stress and subsequent apoptosis, and caspase family proteases are activated during the process of ER stress-mediated apoptosis. In the present study, we showed that thapsigargin (Th), an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), also induced ER stress-mediated apoptosis, and nerve growth factor (NGF) prevented the apoptosis in PC12 cells. We also found that LY 294002, an inhibitor of phosphatidylinositol 3-kinase (PI 3-K), reduced the survival of cells treated with NGF for 24h in the presence of Th. We discovered that the activities of caspase-3, -9 and -12 were increased time-dependently after the treatment with Th, and NGF suppressed the Th-triggered activation of caspase-3, -9 and -12. LY 294002 diminished the effect of NGF on the inactivation of all these caspases. These results indicate that the NGF-induced PI 3-K signaling pathway prevents Th-triggered ER stress-specific apoptosis via inhibition of caspase-mediated apoptotic signal.
authors.affiliation: Faculty of Engineering and High Technology Research Center (HRC), Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan. shimoke@ipcku.kansai-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Shimoke
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Utsumi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shimamura
authors.forename: Harue
authors.initials: H
authors.lastname: Sasaya
authors.forename: Tadao
authors.initials: T
authors.lastname: Oikawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeuchi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D019284:Thapsigargin / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D019284:Thapsigargin; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases