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Cited by 58Pregnancy and preeclampsia studiesReproductive System and PregnancyPeptidase Inhibition and Analysis

Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy

Nomura, Seiji, Ito, Tomomi, Yamamoto, Eiko, Sumigama, Seiji, Iwase, Akira, Okada, Mayumi, Shibata, Kiyosumi, Ando, Hisao +3 more·2005·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
DOI 10.1016/j.bbapap.2005.04.006
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Abstract

Human pregnancy serum and placenta have the ability to degrade uterotonic peptide oxytocin (OT). Placental leucine aminopeptidase (P-LAP), which is also called cystine aminopeptidase, is the only membrane aminopeptidase known to functionally degrade OT as oxytocinase (OTase). P-LAP/OTase hydrolyzes several peptides other than OT including vasopressin and angiotensin III. P-LAP/OTase predicted from cDNA sequence is a type II integral membrane protein, which is converted to a soluble form existing in maternal serum by metalloproteases, possibly ADAM (a disintegrin and metalloproteinase) members. P-LAP/OTase activity increases with normal gestation, while decreases in the patients with preterm delivery and severe preeclampsia. In placenta, P-LAP/OTase is predominantly expressed in differentiated trophoblasts, syncytiotrophoblasts. Activator protein-2 (AP-2) and Ikaros transcription factors play significant roles in exerting high promoter activity of P-LAP/OTase in the trophoblastic cells. Moreover, P-LAP/OTase is transcriptionally regulated in a trophoblast-differentiation-dependent fashion via up-regulation of AP-2, putatively AP-2alpha. P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT and vasopressin.

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Crossref · 10.1016/j.bbapap.2005.04.006

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  • High levels of oxytocinase secreted by the placenta might further contribute to the final serum/plasma oxytocin levels.

    “Moreover, high levels of oxytocinase secreted by the placenta might further contribute to the final serum/plasma OT levels (Nomura et al., 2005).”

    From Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis (2016) · cites this paper as Nomura et al., 2005

  • Overestimation can arise when enzymes are present that degrade oxytocin; the plasma of late pregnant women contains abundant oxytocinase, which inactivates oxytocin by splitting the peptide linkage between the cysteine and tyrosine residues.

    “Overestimation can also arise when enzymes are present that degrade oxytocin. The plasma of late pregnant women contains abundant oxytocinase, which inactivates oxytocin by splitting the peptide linkage between the cysteine and tyrosine residues 102.”

    From Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers (2016) · cites this paper as [102]

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Authors
Nomura, S., Ito, T., Yamamoto, E., Sumigama, S., Iwase, A., Okada, M., Shibata, K., Ando, H., Ino, K., Kikkawa, F., & Mizutani, S.
Affiliations
Nagoya University (JP)
Corresponding author
Nomura, Seiji
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Publisher
Elsevier BV
Published
2005-08
Volume
1751
Issue
1
Pages
19-25
ISSN
1570-9639 (ISSN-L)
DOI
10.1016/j.bbapap.2005.04.006
OpenAlex
W2053877590
Cited by
58
References
66
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 1
FWCI
0.54
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
Keywords
placental leucine aminopeptidase, oxytocinase, placenta, trophoblast differentiation, syncytiotrophoblast, AP2 transcription factor, Ikaros, transcriptional regulation, preterm birth, preeclampsia, vasopressin, angiotensin III
MeSH terms
DNA-Binding Proteins, Female, Fetus, Gene Expression Regulation, Humans, Labor, Obstetric, Membrane Proteins, Oxytocin, Cystinyl Aminopeptidase, Placenta, Pregnancy, Pregnancy Complications, Transcription Factors, Trophoblasts, Protein Structure, Tertiary, Transcription Factor AP-2, Ikaros Transcription Factor

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