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Anti-apoptotic effect of SERM on the amyloid-β-induced apoptosis in PC12

Research Project

Project/Area Number 16591636
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionYamagata University

Principal Investigator

TAKAHASHI Kazuhiro  Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (20292427)

Co-Investigator(Kenkyū-buntansha) KURACHI Hirohisa  Yamagata University, Faculty of Medicine, Professor, 医学部, 教授 (40153366)
IGARASHI Hideki  Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (80333970)
ABE Akiko  Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (30359567)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsestrogen / raloxifene / Alzheimer / β-Amyloid / apoptosis / PC12 / Akt / telomerase / 神経細胞 / 黄体ホルモン / 神経突起
Research Abstract

According to the scheduled research program, we obtained the results using rat pheochromocytoma cell line (PC12) and PC12 cells transfected with the full-length human estrogen receptor (ER) alpha gene (PCER). Raloxifene, like 17beta-estradiol (E2), significantly inhibited Amyloid β-induced apoptosis in PCER cells, but not in a control line of cells transfected with vector DNA alone (PCCON). Since telomerase activity, the level of which is modulated by regulation of telomerase catalytic subunit (TERT) at both the transcriptional and post-transcriptional levels, is known to be involved in suppressing apoptosis in neurons, we examined the effect of E2 and raloxifene on telomerase activity. Although both E2 and raloxifene induced telomerase activity in PCER cells, but not in PCCON cells, treated with Amyloid β, they had no effect on the level of TERT expression. These results suggest that neither E2 nor raloxifene affects the telomerase activity at the transcriptional level. We therefore studied the mechanism by which E2 and raloxifene induce the telomerase activity at the post-transcriptional level. Both E2 and raloxifene induced the phosphorylation of Akt, and pre-treatment with a phosphatidylinositol 3-kinase inhibitor, LY294002, attenuated both E2- and raloxifene-induced activation of the telomerase activity. Moreover, both E2 and raloxifene induced both the phosphorylation of TERT at a putative Akt phosphorylation site and the association of nuclear factor kappaB with TERT. Our findings suggest that and raloxifene exert neuroprotective effects by E2 telomerase activation via a post-transcriptional cascade in an experimental model relevant to Alzheimer's disease.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (2 results)

All 2004

All Journal Article (2 results)

  • [Journal Article] Both estrogen and raloxifene protect against β-amyloid-induced neurotoxicity in estrogen receptor α-transfected PC12 cells by activation of teromerase activity via Akt cascade.2004

    • Author(s)
      Botao Du
    • Journal Title

      Journal of Endocrinology 183

      Pages: 605-615

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Both estrogen and raloxifene protect against β-amyloid-induced neurotoxicity in estrogen receptor α-transfected PC12 cells by activation of teromerase activity via Akt cascade.2004

    • Author(s)
      Botao Du
    • Journal Title

      Journal of Endocrinology 183(3)

      Pages: 605-615

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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