NGF-induced phosphatidylinositol 3-kinase signaling pathway prevents thapsigargin-triggered ER stress-mediated apoptosis in PC12 cells.
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.
Shimoke
Koji
K
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
Kishi
Soichiro
S
Utsumi
Takahiro
T
Shimamura
Yuichi
Y
Sasaya
Harue
H
Oikawa
Tadao
T
Uesato
Shinichi
S
Ikeuchi
Toshihiko
T
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*
D004338:Drug Combinations; D019284:Thapsigargin; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases