title: Genetic deletion of the GATA1-regulated protein α-synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes.
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.
authors.affiliation: Division of Hematology-Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Renella
authors.forename: Julia S
authors.initials: JS
authors.lastname: Schlehe
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: LaVoie
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D017382:Reactive Oxygen Species; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse