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Physiological significance of placental leucine aminopeptidase /oxytocinase at the interface between mother and fetus

Research Project

Project/Area Number 13671705
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NOMURA Seiji  Nagoya University Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20242860)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsoxytocinase / molecular biology / placenta / transcription / cytokine / aminopeptidase / trophoblast / immunoelectron microscopy / アミノペプチターゼ / 分化
Research Abstract

We firstly demonstrated that the region from-297 to-94, which contains four footprint sites (FP1 to FP4), is important for transcription in choriocarcinoma trophoblastic cells. AP-2α, AP-2γ, and Ikaros binding to FP3 (-214 to -183) was important for high promoter activity in these cells. Functional analysis showed that AP-2 is critical for human P-LAP gene expression and Ikaros cooperates with AP-2 to induce maximal promoter activity. This is apparently the first result that Ikaros, initially characterized as a lymphoid-restricted transcriptional factor, is expressed in trophoblasts. P-LAP promoter region contains putative binding sites for cytokine-induced transcription factors. We therefore postulated that inflammatory cytokines suppress P-LAP expression in trophoblasts. Interleukin-1beta (IL-1β) increased P-LAP activity and proteins. Semi-quantitative RT-PCR and Southern blotting showed that IL-1β also increased P-LAP mRNA, which was abrogated by prior exposure to cycloheximide. Luciferase assays did not reveal any regulatory regions that could explain IL-1β-induced P-LAP mRNA accumulation. Immunohistochemical analysis of the human placenta with chorioamnionitis demonstrated prominent P-LAP staining at sites of abundant inflammatory cell infiltration. These findings indicated that prolonged exposure to IL-1β induces P-LAP in the placenta, possibly via other de novo protein synthesis. Transmission immunoelectron microscopy revealed that P-LAP was expressed on the surface of apical microvilli of syncytiotrophoblast cells. Our observation that P-LAP is present on the microvilli, which is a site of interaction between the mother and fetus, suggests possible involvement of these enzymes in cleaving peptide hormones from the fetus and mother in order to regulate bioactivity.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Tomomi Ito: "Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene"Mol Hum Reprod. 7. 887-894 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshinari Katsumata: "Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells"Commun Placenta. 22. 831-836 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomomi Ito: "AP-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene"Biochem Biophys Res. 290. 1048-1053 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikkawa F: "Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation"Placenta. 23. 483-489 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoko Ikoma: "Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells"Mol Hum Reprod. 9. 103-110 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norio Ito: "Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta"Earry Human Dev. 71. 29-37 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野村誠二: "(分担)オキシトシナーゼ"「妊娠の生物学」(永井書店). 349-358 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomomi Ito: "Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene"Mol Hum Reprod. 7. 887-894 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshinari Katsumata: "Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells"Commun Placenta. 22. 831-836 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomomi Ito: "AP-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene"Biochem Biophys Res. 290. 1048-1053 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikkawa F: "Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation"Placenta. 23. 483-489 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoko Ikoma: "Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells"Mol Hum Reprod. 9. 103-110 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norio Ito: "Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta"Earry Human Dev. 71. 29-37 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seiji Nomura: ""Biology of Pregnancy" ; oxytocinase"Nagai-Shoten. 349-358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nomura M: "Differential distribution of placental leucine aminopeptidase/oxytocinase and aminopeptidase A in human trophoblasts of normal placenta and complete hydatidiform mole"Placenta. 23. 631-639 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kikkawa F: "Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation"Placenta. 23. 483-489 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mari Ijima: "Effects of age, hypertension and HRT on serum aminopeptidase A activity"Maturitas. 43. 215-221 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoko Ikoma: "Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells"Mol Hum Reprod. 9. 103-110 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Norio Ito: "Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta"Earry Human Dev. 71. 29-37 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomomi Ito: "Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene"Mol Hum Reprod. 7. 887-894 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshinari Katsumata: "Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells"Placenta. 22. 831-836 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomomi Ito: "AP-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene"Biochem Biophys Res Commun. 290. 1048-1053 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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