Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol

PLoS One. 2014 Jun 12;9(6):e99421. doi: 10.1371/journal.pone.0099421. eCollection 2014.


Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Estradiol / pharmacology*
  • Female
  • Hot Temperature
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Necrosis
  • Oxidative Stress / drug effects
  • Placental Extracts / pharmacology*
  • Sus scrofa
  • alpha-Fetoproteins / metabolism*


  • Antioxidants
  • Biomarkers
  • Placental Extracts
  • alpha-Fetoproteins
  • Estradiol
  • Hydrogen Peroxide

Grant support

This work was supported by grants from the National Research Foundation (NRF) funded by the Korean government (MEST) (No. 2010-0020348) (No. 2013M3A9D3045880) and by the Bio-Industry Technology Development Program, Ministry of Agriculture, Food and Rural Affairs (No. 312062-05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.