Dopamine induces platelet production from megakaryocytes via oxidative stress-mediated signaling pathways

Platelets. 2018 Nov;29(7):702-708. doi: 10.1080/09537104.2017.1356451. Epub 2017 Nov 9.

Abstract

Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis.

Keywords: Dopamine; megakaryocyte; oxidative stress; platelet; thrombopoiesis.

MeSH terms

  • Animals
  • Apoptosis
  • Blood Platelets / metabolism*
  • Caspase 3 / metabolism
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Flow Cytometry
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism*
  • Mice
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*
  • Thrombopoiesis* / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Reactive Oxygen Species
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Dopamine