title: The role of red blood cell S-nitrosation in nitrite bioactivation and its modulation by leucine and glucose.
abstract: Previous work has shown that red blood cells (RBCs) reduce nitrite to NO under conditions of low oxygen. Strong support for the ability of red blood cells to promote nitrite bioactivation comes from using platelet activation as a NO-sensitive process. Whereas addition of nitrite to platelet rich plasma in the absence of RBCs has no effect on inhibition of platelet activation, when RBCs are present platelet activation is inhibited by an NO-dependent mechanism that is potentiated under hypoxia. In this paper, we demonstrate that nitrite bioactivation by RBCs is blunted by physiologically-relevant concentrations of nutrients including glucose and the important signaling amino acid leucine. Our mechanistic investigations demonstrate that RBC mediated nitrite bioactivation is largely dependent on nitrosation of RBC surface proteins. These data suggest a new expanded paradigm where RBC mediated nitrite bioactivation not only directs blood flow to areas of low oxygen but also to areas of low nutrients. Our findings could have profound implications for normal physiology as well as pathophysiology in a variety of diseases including diabetes, sickle cell disease, and arteriosclerosis.
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Wajih
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Pragna
authors.initials: P
authors.lastname: Shetty
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA; Translational Science Center, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Hanzhi
authors.initials: H
authors.lastname: Wu
authors.affiliation: Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Hogg
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 901 19th St. South, BMRII 532, Birmingham, AL 35294, USA.
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.affiliation: Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Furdui
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA; Translational Science Center, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: shapiro@wfu.edu.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
mesh_terms: D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D015538:Nitrosation; D010100:Oxygen / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D009573:Nitrites; D009569:Nitric Oxide; D007930:Leucine; D005947:Glucose; D010100:Oxygen
keywords: Glucose; Hemoglobin; Leucine; Nitric oxide; Nitrite; Red blood cells