Molecular mechanisms regulating lysophosphatidylcholine acyltransferase 1 (LPCAT1) in human pregnancy.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8006349 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3102 (Electronic) Linking ISSN: 01434004 NLM ISO Abbreviation: Placenta Subsets: MEDLINE
    • Publication Information:
      Publication: <2010- > : Amsterdam : Elsevier
      Original Publication: London W.B. Saunders.
    • Subject Terms:
      Gene Expression Regulation*; 1-Acylglycerophosphocholine O-Acyltransferase/*metabolism ; Mitochondria/*metabolism ; Placenta/*metabolism ; Pregnancy Trimester, Third/*metabolism; 1-Acylglycerophosphocholine O-Acyltransferase/genetics ; Cell Line ; Cell Nucleus/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Female ; Humans ; Mitochondria/genetics ; Pregnancy ; Pregnancy Trimester, Third/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism
    • Abstract:
      Introduction: Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) is necessary for surfactant production in fetal lungs. Mechanisms responsible for its regulation during gestation remain to be elucidated. Our goal is to evaluate molecular mechanisms regulating LPCAT1 expression during gestation and after glucocorticoid administration.
      Methods: Placentas throughout gestation were assayed for LPCAT1 protein levels. A placental cell line, HTR-8/SVneo (HTR), was used as a model to test the effects of placental oxygen tension found during pregnancy as well as the effects of dexamethasone used therapeutically in the clinic.
      Results: LPCAT1 protein levels are maximal in late third trimester placental samples and are expressed strongly on the basal plate. LPCAT1 was maximally upregulated at 4% O 2 (P < 0.01), corresponding to oxygen tension found in placenta at term. Mitochondrial nuclear retrograde regulator 1 (MNRR1), a bi-organellar (mitochondria and nucleus) regulator, transcriptionally activates LPCAT1. Antenatal corticosteroids (ACS) upregulate LPCAT1, at least in part, by an MNRR1-dependent pathway. HTR cells treated with 25 nM dexamethasone for 24 h exhibited a 2-fold increase in LPCAT1 levels compared to controls. In MNRR1 knockout cells, the response to ACS is significantly blunted.
      Discussion: LPCAT1 appears to be induced by MNRR1. Hypoxia and corticosteroids increase LPCAT1 expression through an MNRR1 dependent pathway. LPCAT1 protein levels can be measured in maternal plasma and rise throughout gestation and in response to ACS.
      (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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    • Grant Information:
      K12 HD001254 United States HD NICHD NIH HHS
    • Contributed Indexing:
      Keywords: Hypoxia; LPCAT1; Lung maturation; Lysophosphatidylcholine acyltransferase 1; Pregnancy; Steroids
    • Accession Number:
      0 (CHCHD2 protein, human)
      0 (DNA-Binding Proteins)
      0 (Transcription Factors)
      EC 2.3.1.23 (1-Acylglycerophosphocholine O-Acyltransferase)
      EC 2.3.1.23 (Lpcat1 protein, human)
    • Publication Date:
      Date Created: 20210222 Date Completed: 20211231 Latest Revision: 20220302
    • Publication Date:
      20240829
    • Accession Number:
      PMC8026739
    • Accession Number:
      10.1016/j.placenta.2021.02.005
    • Accession Number:
      33618181