Identification of molecular target proteins related to cardiac function in fetal rat tissues after antenatal glucocorticoid administration using a proteomics approach

  • Yoshimitsu Tsuzuki, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Kentaro Asoh, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Yuko Takeba, Department of Pharmacology, St.Marianna University School of Medicine, Japan
  • Yachiyo Kurihara, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Kenzirou Gotoh, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Masaki Arima, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Masanori Mizuno, Department of Pediatrics, St.Marianna University School of Medicine, Japan
  • Yasushi Koitabashi, Department of Pediatrics, St.Marianna University School of Medicine, Japan

  • Antenatal glucocorticoid therapy has been shown to improve acute conditions including infant respiratory distress syndrome and reduce mortality, although little known is about the effects on cardiac function-related factors in the fetus or neonate. We investigated whether cardiac function-related factors are altered in cardiac tissues of fetuses and neonates born to pregnant rats administered glucocorticoid.

    Dexamethasone 1 mg/kg s.c. or vehicle was administered for 2 days to pregnant rats on days 17 and 18 or 19 and 20 of gestation, and cardiac tissues of 19- and 21-day fetuses and 1-, 3-, and 5-day neonates were analyzed using a proteomic technique with liquid chromatography-mass spectrometry/mass spectrometry.

    The five proteins alpha-enolase, creatine kinase-M type, beta-tubulin, troponin T, and ATP synthase beta-chain were identified.
    In Western blot analysis, the glycolytic enzyme enolase was increased significantly in the 19-day and 21-day fetal groups after antenatal dexamethasone administration compared with the respective control groups. Levels of cAMP as a metabolic product of ATP were significantly increased in the 19-day and 21-day fetal groups after antenatal dexamethasone. Immunohistologically, the cross-sectional area of ventricular myocardium was significantly increased in the 21-day fetal and 1-day neonatal dexamethasone groups. The increase in heart size might have resulted from increased alpha-enolase levels in cardiac tissues with antenatal glucocorticoid administration.

    These results suggest that antenatal glucocorticoid therapy may accelerate cardiac development of the preterm heart.