Nerve growth factor attenuates endoplasmic reticulum stress-mediated apoptosis via suppression of caspase-12 activity |
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Authors: | Shimoke Koji Amano Hisayuki Kishi Soichiro Uchida Hitoshi Kudo Motoshige Ikeuchi Toshihiko |
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Affiliation: | Laboratory of Neurobiology, Faculty of Engineering and High Technology Research Center (HRC), Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680. shimoke@ipcku.kansai-u.ac.jp |
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Abstract: | Following endoplasmic reticulum (ER) stress, which occurs via inhibition of the glycosylation of newly synthesized proteins, caspase family proteins are activated to promote ER stress-mediated apoptosis. Here we report that nerve growth factor (NGF) suppressed the ER stress-mediated apoptosis in tunicamycin-treated PC12 cells through an extensive decrease of the caspase-3/-9/-12 activity. Detailed analysis of the mechanism underlying the NGF-mediated cell survival revealed that the activities of all seriate caspases were reduced through the phosphatidylinositol 3-kinase (PI3-K) signaling pathway induced by NGF. Moreover, we found that the activity of c-Jun N-terminal kinase (JNK) was not essential for the tunicamycin-induced apoptosis of PC12 cells. These results demonstrate that the inactivation of caspase-12 via the NGF-mediated PI3-K signaling pathway leads to inactivation of the caspase cascade including caspase-3 and -9. |
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