Regulation of ER stress response by insulin signaling

• Project/Area Number: 22590553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: INAGEDA Kiyoshi 東京女子医科大学, 医学部, 助教 (90281659)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: インスリン / 小胞体ストレス / GRP78/Bip / ATF4 / アポトーシス / 神経保護 / GRP78 / SH-SY5Y

Research Abstract

The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein level through PI-3 kinase/AKT pathway. The increase of ATF4 protein by insulin was not due to transcriptional or transational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation.

Research Products

• [Journal Article] Cadmium induces phosphorylation and stabilization of c-Fos in HK-2 renal proximal tubular cells (2011)
  • Author(s): Iwatsuki M, Inageda K, Matsuoka M.
  • Journal Title: Toxicol Appl Pharmacol. Volume: 251 Pages: 209-16
  • Peer Reviewed
• [Journal Article] Cadmium induces phosphorylation and stabilization of c-Fos in HK-2 renal proximal tubular cells (2011)
  • Author(s): Iwatsuki M, Inageda K, Matsuoka M
  • Journal Title: Toxicol.Appl.Pharmacol. Volume: 251 Issue: 3 Pages: 209-216
  • DOI: 10.1016/j.taap.2010.12.015
  • Peer Reviewed
• [Journal Article] Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells (2010)
  • Author(s): Inageda K
  • Journal Title: FEBS Lett. Volume: 584 Pages: 3649-54
  • Peer Reviewed
• [Journal Article] Insulin modulates induction of glucose regulated protein 78 during endo plasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells (2010)
  • Author(s): 稲毛田清
  • Journal Title: FEBS Letters Volume: 584 Pages: 3649-3654
  • Peer Reviewed
• [Presentation] HeLa 細胞におけるトリブチルスズ曝露によるインターロイキン-8(IL-8)誘導 (2012)
  • Author(s): 稲毛田清、松岡雅人
  • Organizer: 第7回臨床ストレス応答学会大会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-24
• [Presentation] HeLa 細胞におけるトリブチルスズ曝露によるインターロイキン-8(IL-8)誘導 (2012)
  • Author(s): 稲毛田清、 松岡雅人
  • Organizer: 第82回日本衛生学会総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-25
• [Presentation] HeLa細胞におけるトリブチルスズ暴露によるインターロイキン(IL-8)誘導 (2012)
  • Author(s): 稲毛田清、松岡雅人
  • Organizer: 第82回日本衛生学学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-25
• [Presentation] HeLa 細胞におけるトリブチルスズ曝露によるインターロイキン-8(IL-8)誘導 (2012)
  • Author(s): 稲毛田清、松岡雅人
  • Organizer: 臨床ストレス応答学会
  • Place of Presentation: 東京
• [Presentation] SH-SY5Y 細胞における小胞体ストレス応答に対するインスリンの効果 (2011)
  • Author(s): 稲毛田清
  • Organizer: 第10回生命科学研究会
  • Place of Presentation: 高崎
  • Year and Date: 2011-06-25
• [Presentation] SY5Y細胞における小胞体ストレス応答に対するインスリンの効果 (2011)
  • Author(s): 稲毛田清
  • Organizer: 第10回生命科学研究会
  • Place of Presentation: 高崎
  • Year and Date: 2011-06-25
• [Presentation] SH-SY5Y 細胞におけるインスリンによる小胞体ストレス応答の修飾 (2011)
  • Author(s): 稲毛田清
  • Organizer: 第81回日本衛生学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-28
• [Presentation] ヒト神経芽細胞腫細胞におけるインスリンによる小胞体ストレス応答の修飾ーATF4 を介する GRP78 誘導 (2010)
  • Author(s): 稲毛田清
  • Organizer: 第5回臨床ストレス応答学会大会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-19
• [Presentation] ヒト神経芽細胞腫細胞におけるインスリンによる小胞体ストレス応答の修飾-ATF4を介するGRP78誘導 (2010)
  • Author(s): 稲毛田清
  • Organizer: 臨床ストレス応答学会
  • Place of Presentation: 徳島大学附属病院西病棟11階日亜メディカルホール(徳島県)
  • Year and Date: 2010-11-19