Genetic deletion of the GATA1-regulated protein α-synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes

Am J Hematol. 2014 Oct;89(10):974-7. doi: 10.1002/ajh.23796. Epub 2014 Jul 21.

Abstract

α-Synuclein is highly expressed in neural tissue and during erythropoiesis, where the key erythroid regulator GATA1 has been found to modulate its expression. While specific α-synuclein (SNCA) mutations are known to cause autosomal dominant familial Parkinson's disease, its wild-type function remains under debate. To investigate the role of α-synuclein in murine hematopoiesis and erythropoiesis, we utilized Snca knock-out mice and analyzed erythroid compartments for maturation defects, in vivo erythrocyte survival, and erythrocyte-based reactive oxygen species (ROS) and nitric oxide synthase (NOS) levels. Our findings show that while bone marrow and spleen erythropoiesis and peripheral blood erythrocyte survival in Snca(-/-) mice was comparable to controls, the levels of ROS and of NOS-2 were significantly decreased in mature erythrocytes in these animals. These results indicate a role for α-synuclein in regulating oxidative stress in erythrocytes in vivo and could open new avenues for the investigation of its function in non-neural tissue.

MeSH terms

  • Animals
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Erythropoiesis / physiology*
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism*
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Reactive Oxygen Species
  • Snca protein, mouse
  • alpha-Synuclein
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse