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Updated: Mar 31, 2026

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
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Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

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Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling

Fan Sun1,2, Xu-Ping Ding1, Shi-Min An1,3

  • 1Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Scientific Reports
|October 31, 2015
PubMed

Insights

Embryonic stem cells are vulnerable to DNA damage and apoptosis from adrenergic stress via the β2 adrenergic receptor pathway. This signaling cascade involves reactive oxygen species (ROS) and impacts genome integrity.

Area of Science:

  • Stem cell biology
  • Molecular toxicology
  • Signaling pathways

Background:

  • Embryonic pluripotent cells require stringent genome integrity.
  • The impact of adrenergic stress on these cells is largely unknown.
  • Adrenergic stress can induce DNA damage in somatic cells.

Purpose of the Study:

  • To investigate the susceptibility of embryonic stem cells to adrenergic stress.
  • To elucidate the signaling pathway involved in adrenergic-induced DNA damage.
  • To determine the role of reactive oxygen species (ROS) in this process.

Main Methods:

  • Treatment of embryonic stem cells and embryonal carcinoma stem cells with adrenergic agonists (adrenaline, noradrenaline, isoprenaline).
  • Utilizing β2 receptor-coupled signaling molecules and selective β2 receptor blockade.
  • Employing RNA interference targeting β2 receptors.
  • Measuring DNA damage, apoptosis, and intracellular ROS accumulation.

Main Results:

  • Adrenergic agonists induced DNA damage and apoptosis in embryonic stem cells and embryonal carcinoma stem cells.
  • The effects were mediated through the β2 adrenergic receptor/adenylate cyclase/cAMP/PKA signaling pathway.
  • Adrenergic stimulation led to ROS accumulation, which was responsible for the DNA damage.
  • Blocking β2 receptors or quenching ROS prevented the observed damage and apoptosis.

Conclusions:

  • Embryonic stem cells are susceptible to DNA damage and apoptosis induced by adrenergic stress.
  • The β2 adrenergic receptor signaling pathway plays a critical role in mediating these effects.
  • ROS accumulation is a key mechanism linking adrenergic stress to genotoxicity in these cells.
  • Understanding this pathway offers insights into stem cell regulation and pathophysiology.

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