[The relationship between P53 and hypoxia-inducible transcription factor-1alpha in the placenta of patient with intrahepatic cholestasis of pregnancy under acute hypoxic condition]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Nov;37(6):901-3, 942.
[Article in Chinese]

Abstract

Objective: Owing to the molecular mechanisms unexplored yet to fetal hypoxia signaling in the intrahepatic cholestasis of pregnancy (ICP), and therefore we intend to investigate the significant expression of the hypoxia-inducible transcription factor-1alpha (HIF-1alpha) in placenta of pregnant women with ICP during hypoxia.

Methods: The villous placenta tissues were in vitro cultured under hypoxia condition. The immuno-histochemistry technique was applied to probe the HIF-1alpha and P53 expressions in placentas of pregnant women and patient with ICP.

Results: Under the condition of normal concentration oxygen, P53 was highly expressed in the placenta of pregnant women with ICP (P < 0.01), however the HIF-1alpha expression was not up to higher than in normal control. Under the condition of lower concentration oxygen (2% O2), the HIF-1alpha and P53 expressions were detected from the placental villous tissues cultured for 4 h of normal control and patient with ICP, and with HIF-1alpha and P53 proteins increased in the placenta of pregnant women with ICP (P < 0.05 and P < 0.001 respectively). Whatever was hypoxia condition, P53 protein got always a high expression, and had a positive correlation with HIF-1alpha expression in ICP (P < 0.01).

Conclusion: Under hypoxic conditions, high increase of HIF-1alpha may influence the increase of P53 directly, which may be one of the hypoxia pathogenesis factors in ICP. The fetal hypoxia and stillbirth may be the results of unbalance of HIF-1alpha and P53 which induced apoptosis under hypoxia condition.

Publication types

  • English Abstract

MeSH terms

  • Case-Control Studies
  • Cell Hypoxia
  • Cell Nucleus / metabolism
  • Cholestasis, Intrahepatic / metabolism*
  • Cholestasis, Intrahepatic / pathology
  • Cytoplasm / metabolism
  • Female
  • Fetus / cytology
  • Gene Expression Regulation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Placenta / metabolism*
  • Placenta / pathology*
  • Pregnancy
  • Pregnancy Complications / metabolism*
  • Pregnancy Complications / pathology
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tumor Suppressor Protein p53