Comparison of protective mechanisms of nicotine and NGF against neuronal ER stress

• Project/Area Number: 21570152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kansai University
• Principal Investigator: IKEUCHI Toshihiko 関西大学, 化学生命工学部, 教授 (20093362)
• Co-Investigator(Kenkyū-buntansha): SHIMOKE Koji 関西大学, 化学生命工学部, 准教授 (10351496)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞情報伝達機構 / 神経変性疾患 / 神経細胞 / 細胞内シグナル伝達機構 / 小胞体ストレス / ニコチン / ニューロトロフィン / 神経成長因子 / 分子シャペロン

Research Abstract

We compared protective mechanisms of nicotine and NGF(nerve growth factor) against ER stress in PC12 cells as a model neuron. Nicotine suppressed ER stress at the earliest stage, but NGF protected it through enhanced expression of ER chaperon GRP78. In addition, forskolin which increases cAMP level protected it at the earliest stage as nicotine. Therefore, the treatment of cells with all three compounds(or factors) is considered to have an additive or cooperative protective effect against neuronal ER stress.

Research Products

• [Journal Article] Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells (2012)
  • Author(s): Sasaya, H., Yasuzumi, K., Maruoka, H., Fujita, A., Kato, Y., Waki, T., Shimoke, K. and Ikeuchi, T
  • Journal Title: Advances in Biological Chemistry Volume: 2 Pages: 92-105
  • Peer Reviewed
• [Journal Article] New orally bioavailable 2-aminobenzamide-type histone deacetyase inhibitor promotes neurite outgrowth via histone H3 modification in PC12 cells : a possible therapeutic candidate for neuronal diseases (2012)
  • Author(s): Maruoka, H., Hosokawa, R., Hirata, Y., Kawa, H., Okamoto, K., Waki, T., Uesato, S., Ikeuchi, T. and Shimoke, K
  • Journal Title: Journal of Bioengineering and Biomedical Sciences Volume: S5 Pages: 1-5
  • Peer Reviewed
• [Journal Article] New orally bioavailable 2-aminobenzamide-type histone deacetyase inhibitor promotes neurite outgrowth via histone H3 modification in PC12 cells : a possible therapeutic candidate for neuronal diseases (2012)
  • Author(s): 丸岡弘規
  • Journal Title: Journal of Bioengineering and Biomedical Sciences Volume: S5巻 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells (2012)
  • Author(s): 笹谷晴恵
  • Journal Title: Advances in Biological Chemistry Volume: 2巻 Issue: 02 Pages: 92-105
  • DOI: 10.4236/abc.2012.22012
  • Peer Reviewed
• [Journal Article] Low-molecular-weight compounds having neurotrophic activity in cultured PC12 cells and neurons (2011)
  • Author(s): Maruoka, H., Sasaya, H., Sugihara, K., Shimoke, K. and Ikeuchi, T
  • Journal Title: Journal of Biochemistry Volume: 150 Pages: 473-475
  • NAID: 10030588353
  • Peer Reviewed
• [Journal Article] Appearance of nuclear-sorted caspase-12 fragments in cerebral cortical and hippocampal neurons in rats damaged by autologous blood clot embolic brain infarctions (2011)
  • Author(s): Shimoke, K., Matsuki, Y., Fukunaga, K., Matsumura, Y., Fujita, E., Sugihara, K., Nobuhara, M., Maruoka, H., Ikeuchi, T. and Kudo, M
  • Journal Title: Cellular and Molecular Neurobiology Volume: 31 Pages: 795-802
  • Peer Reviewed
• [Journal Article] Nerve growth factor for cell survival during endoplasmic reticulum stress in PC12 cells (2011)
  • Author(s): Shimoke, K., Sasaya, H. and Ikeuchi, T
  • Journal Title: The Unfolded Protein Response and Cellular Stress, Part B Volume: 490 Pages: 53-70
  • Peer Reviewed
• [Journal Article] Appearance of nuclear-sorted caspase-12 fragments in cerebral cortical and hippocampal neurons in rats damaged by autologous blood clot embolic brain infarctions (2011)
  • Author(s): 下家浩二
  • Journal Title: Cellular and Molecular Neurobiology Volume: 31巻 Issue: 5 Pages: 795-802
  • DOI: 10.1007/s10571-011-9687-0
  • Peer Reviewed
• [Journal Article] Low-molecular-weight compounds having neurotrophic activity in cultured PC12 cells and neurons (2011)
  • Author(s): 丸岡弘規
  • Journal Title: Journal of Biochemistry Volume: 150巻 Issue: 5 Pages: 473-475
  • DOI: 10.1093/jb/mvr113
  • Peer Reviewed
• [Journal Article] Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells. (2011)
  • Author(s): 丸岡弘規
  • Journal Title: Journal of Biochemistry Volume: 148巻 Pages: 93-101
  • Peer Reviewed
• [Journal Article] Analysis of the role of nerve growth factor in promoting cell survival during endoplasmic reticulum stress in PC12 cells. (2011)
  • Author(s): 下家浩二
  • Journal Title: Methods in Enzymology Volume: 490 Pages: 53-70
  • Peer Reviewed
• [Journal Article] Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells (2010)
  • Author(s): Maruoka, H., Sasaya, H., Shimamura, Y., Nakatani, Y., Shimoke, K. and Ikeuchi, T
  • Journal Title: Journal of Biochemistry Volume: 148 Pages: 93-101
  • NAID: 10027877262
  • Peer Reviewed
• [Journal Article] Site-directed mutagenesis of rice serine racemase : evidence that Glu219 and Asp225 mediate the effects of Mg++on the acfivity (2010)
  • Author(s): Gogami, Y., Kobayashi, A., Ikeuchi, T. and Oikawa, T
  • Journal Title: Chemistry and Biodiversity Volume: 7 Pages: 1579-1590
  • Peer Reviewed
• [Journal Article] Nerve growth factor attenuates 2-deoxy-D-glucose-triggered endoplasmic reticulum stress-mediated apoptosis via enhanced expression of GRP78 (2010)
  • Author(s): Kishi, S., Shimoke, K., Nakatani, Y., Shimada, T., Okumura, N., Nagai, K., Shin-ya, K. and Ikeuchi, T
  • Journal Title: Neuroscience Research Volume: 66 Pages: 14-21
  • Peer Reviewed
• [Journal Article] Nerve growth factor attenuates 2-deoxy-D-glucose-triggered endoplasmic reticulum stress-mediated apoptosis via enhanced expression of GRP78 (2010)
  • Author(s): 岸宗一郎
  • Journal Title: Neuroscience Research 66巻 Pages: 14-21
  • Peer Reviewed
• [Journal Article] Site-directed mutagenesis of rice serine racemase : evidence that Glu21 and Asp225 mediate the effects of Me++ on the acfivity (2010)
  • Author(s): 郷上佳孝
  • Journal Title: Chemistry and Biodiversity (印刷中)
  • Peer Reviewed
• [Journal Article] Protection from ER stress-mediated apoptosis by the neurotrophins (2009)
  • Author(s): Shimoke, K., Fukunaga, K., Matsumura, Y., Kudo, M. and Ikeuchi, T
  • Journal Title: Current Topics in Biochemical Research Volume: 11 Pages: 19-28
• [Journal Article] Isolation and characterization of novel bisphenol-A-degrading bacteria from soils (2009)
  • Author(s): Matsumura Y., Hosokawa C., Sasaki-Mori M., Akahira A., Fukunaga K., Ikeuchi T., Oshiman K. and Tsuchido T
  • Journal Title: Biocontrol Science Volume: 14 Pages: 161-169
  • NAID: 10027043869
  • Peer Reviewed
• [Journal Article] Isolation and characterization of novel bisphenol-A-degrading bacteria from soils (2009)
  • Author(s): 松村吉信
  • Journal Title: Biocontrol Science 14 Pages: 161-169
  • Peer Reviewed
• [Presentation] Subtype specific mechanisms of neurite outgrowth and cell survival by HDAC families in PC12 cells (2011)
  • Author(s): 杉原健介
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] Subtype specific mechanisms of neurite outgrowth and cell survival by HDAC families in PC12 cells (2011)
  • Author(s): 杉原健介
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] Nerve growth factor decreases ER stress-mediated apoptosis through refolding unfolded protein structure by glucose-regulated protein 78 in PC12 cells (2011)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: Walter Washington Convention Center(Washington DC, USA)
  • Year and Date: 2011-11-14
• [Presentation] Nerve growth factor decreases ER stress-mediated apoptosis through refolding unfolded protein structure by glucose-regulated protein 78 in PC12 cells (2011)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: Walter E.Washington Convention Center (Washington DC, USA)
  • Year and Date: 2011-11-14
• [Presentation] Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells (2011)
  • Author(s): 安栖和也
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Forskolin suppresses ER stress-mediated apoptosis via enhanced expression of GRP78 by non-PI3-kinase pathway in PC12 cells (2011)
  • Author(s): 藤田亜弓
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Involvement of nur77 gene product in neurite outgrowth induced by dibutyryl cAMP and trichostatin A in PC12 cells (2011)
  • Author(s): 河広倫
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Involvement of nur77 gene product in neurite outgrowth induced by dibutyryl cAMP and trichostatin A in PC12 cells (2011)
  • Author(s): 河広倫
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] Forskolin suppresses ER stress-mediated apoptosis via enhanced expression of GRP78 by non-PI3-kinase pathway in PC12 cells (2011)
  • Author(s): 藤田亜弓
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells (2011)
  • Author(s): 安栖和也
  • Organizer: 日本生化学会年会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] Mechanism by which HDAC inhibitors suppress ER stress-induced apoptosis (2011)
  • Author(s): 細川龍
  • Organizer: Japanese Society for Epigenetics
  • Place of Presentation: KKRホテル熊本
  • Year and Date: 2011-05-19
• [Presentation] Mechanism by which HDAC inhibitors suppress ER stress-induced apoptosis (2011)
  • Author(s): 細川龍
  • Organizer: Japanese Society for Epigenetics
  • Place of Presentation: KKRホテル熊本(熊本)
  • Year and Date: 2011-05-19
• [Presentation] Comparison between apoptosis-inducing effect and estrogen-like effect ofendocrine-disrupting chemicals in cultured PC12 cells (2010)
  • Author(s): 笹谷晴恵
  • Organizer: 日本環境ホルモン学会研究発表会
  • Place of Presentation: 東京大学
  • Year and Date: 2010-12-16
• [Presentation] Comparison between apoptosis-inducing effect and estrogen-like effect of endocrine-disrupting chemicals in cultured PC12 cells. (2010)
  • Author(s): 笹谷晴恵
  • Organizer: 日本環境ホルモン学会研究発表会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-12-16
• [Presentation] Comparison between apoptosis-inducing effect and estrogen-like effect ofendocrine-disrupting chemicals in cultured PC12 cells (2010)
  • Author(s): 笹谷晴恵
  • Organizer: Congress of Biochemistry and Molecular Biology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-09
• [Presentation] Comparison between apoptosis-inducing effect and estrogen-like effect of endocrine-disrupting chemicals in cultured PC12 cells. (2010)
  • Author(s): 笹谷晴恵
  • Organizer: Congress of Biochemistry and Molecular Biology 2010
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-12-09
• [Presentation] Nerve growth factor decreases ER stress-induced apoptosis through down-regulation of PUMA and Bim in PC12 cells (2010)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-13
• [Presentation] Nerve growth factor decreases ER stress-induced apoptosis through down-regulation of PUMA and Bim in PC12 cells. (2010)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: Convention Center (San Diego, USA)
  • Year and Date: 2010-11-13
• [Presentation] Regulatory effect of NGF on apoptosis and autophagy induced by tunicamycin with chloroquine in PC12 cells (2010)
  • Author(s): 入船宏美
  • Organizer: 日本神経化学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-09-02
• [Presentation] Regulatory effect of NGF on apoptosis and autophagy induced by tunicamycin with chloroquine in PC12 cells. (2010)
  • Author(s): 入船宏美
  • Organizer: 日本神経化学会年会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-09-02
• [Presentation] Action of NGF signal on autophagy-related proteins (2010)
  • Author(s): 入船宏美
  • Organizer: Spring Symposium of Japanese Society for Molecular Biology
  • Place of Presentation: ホテル松島大観荘
  • Year and Date: 2010-06-07
• [Presentation] Action of NGF signal on autophagy-related proteins. (2010)
  • Author(s): 入船宏美
  • Organizer: Spring Symposium of Japanese Society for Molecular Biology
  • Place of Presentation: ホテル松島大観荘(宮城県)
  • Year and Date: 2010-06-07
• [Presentation] BAX oligomerization promotes ER stress-mediated apoptosis and nerve growth factor prevents it in PC12 cells (2009)
  • Author(s): 島田貴史
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] BAX oligomerization promotes ER stress-mediated apoptosis and nerve growth factor prevents it in PC12 cells (2009)
  • Author(s): 島田貴史
  • Organizer: 日本分子生物学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-12-10
• [Presentation] Nerve growth factor enhances GRP78 expression only under the condition of ER stress in PC12 cells (2009)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: Convention Center
  • Year and Date: 2009-11-13
• [Presentation] Nerve growth factor enhances GRP78 expression only under the condition of ER stress in PC12 cells (2009)
  • Author(s): 下家浩二
  • Organizer: Society for Neuroscience
  • Place of Presentation: Convention Center(Chicago)
  • Year and Date: 2009-11-13
• [Presentation] Analysis of GRP78 promoter region involved in NGF-induced up-regulation during suppression of ER stress-mediated apoptosis in PC12 cells (2009)
  • Author(s): 中谷陽介
  • Organizer: 日本生化学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-23
• [Presentation] Analysis of GRP78 promoter region involved in NGF-induced up-regulation during suppression of ER stress-mediated apoptosis in PC12 cells (2009)
  • Author(s): 中谷陽介
  • Organizer: 日本生化学会大会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2009-10-23
• [Presentation] Nerve growth factor prevents ER stress-induced apoptosis via down-regulation of PUMA expression in PC12 cells (2009)
  • Author(s): 下家浩二
  • Organizer: 17th ECDO Euroconference on Apoptosis
  • Place of Presentation: Pasteur Institute
  • Year and Date: 2009-09-23
• [Presentation] Nerve growth factor prevents ER stress-induced apoptosis via down-regulation of PUMA expression in PC12 cells (2009)
  • Author(s): 下家浩二
  • Organizer: 17th ECDO Euroconference on Apoptosis
  • Place of Presentation: Pasteur Institute(Paris)
  • Year and Date: 2009-09-23
• [Presentation] Nerve growth factor promotes GRP78 expression only under the condition of ER stress (2009)
  • Author(s): 下家浩二
  • Organizer: 日本神経化学会年会
  • Place of Presentation: ホテル天坊
  • Year and Date: 2009-06-24
• [Presentation] Nerve growth factor promotes GRP78 expression only under the condition of ER stress (2009)
  • Author(s): 下家浩二
  • Organizer: 日本神経化学会大会
  • Place of Presentation: ホテル天坊(群馬伊香保)
  • Year and Date: 2009-06-24
• [Remarks]
  • URL: http://neurobio.life-bio.kansai-u.ac.jp/
• [Remarks]
  • URL: http://neurobio.life-bio.kansai-u.ac.jp/
• [Remarks]
  • URL: http://neurobio.life-bio.kansai-u.ac.jp/
• [Remarks]
  • URL: http://neurobio.life-bio.kansai-u.ac.jp/
• [Patent(Industrial Property Rights)] 神経変性疾患治療薬のスクリーニング方法 (2010)
  • Inventor(s): 下家浩二、上里新一、池内俊彦
  • Industrial Property Rights Holder: 関西大学
  • Industrial Property Number: 2010-245306
  • Filing Date: 2010-11-01
• [Patent(Industrial Property Rights)] 甲虫を用いた社会性に関与する生理活性物質を創出する方法 (2009)
  • Inventor(s): 下家浩二、池内俊彦
  • Industrial Property Rights Holder: 関西大学
  • Industrial Property Number: 2009-136463
  • Filing Date: 2009-06-05
• [Patent(Industrial Property Rights)] 甲虫を用いた社会性に関与する生理活性物質を創出する方法 (2009)
  • Inventor(s): 下家浩二, 池内俊彦
  • Industrial Property Rights Holder: 関西大学
  • Industrial Property Number: 2009-136463
  • Filing Date: 2009-06-05