Neuroprotective Effects of 17β-Estradiol against Thrombin-Induced Apoptosis in Primary Cultured Cortical Neurons

Pharmacology. 2015;96(5-6):284-9. doi: 10.1159/000440961. Epub 2015 Oct 27.

Abstract

Aims: 17β-estradiol (E2) is a powerful neuroprotective agent in the central nervous system; however, little is known about its effects on intracerebral hemorrhage. This study examined the effects of E2 on thrombin-induced apoptosis in vitro and investigated the potential mechanisms.

Methods: Primary cultured cortical neurons were treated with E2 or vehicle and then the cells were exposed to thrombin. Neuronal apoptosis was assessed by flow cytometry. The phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were assayed by western blot.

Results: Consequently, we found that E2 has significantly reduced the apoptosis in thrombin-treated neurons. E2 also exhibited a downregulation in the ratio of Bax/Bcl-2, caspase-3 and p-JNK. However, E2 had little effect on p-ERK1/2 proteins activation.

Conclusion: Taken together, E2 has shown neuroprotective effects on thrombin-induced neuronal apoptosis, and the molecular mechanisms may correlate with the inhibition of the JNK signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Blotting, Western
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Estradiol / pharmacology*
  • Flow Cytometry
  • MAP Kinase Signaling System / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Primary Cell Culture
  • Rats
  • Thrombin / toxicity*

Substances

  • Apoptosis Regulatory Proteins
  • Neuroprotective Agents
  • Estradiol
  • Thrombin