title: Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivo.
abstract: The β93 cysteine (β93Cys) residue of hemoglobin is conserved in vertebrates but its function in the red blood cell (RBC) remains unclear. Because this residue is present at concentrations more than 2 orders of magnitude higher than enzymatic components of the RBC antioxidant network, a role in the scavenging of reactive species was hypothesized. Initial studies utilizing mice that express human hemoglobin with either Cys (B93C) or Ala (B93A) at the β93 position demonstrated that loss of the β93Cys did not affect activities nor expression of established components of the RBC antioxidant network (catalase, superoxide dismutase, peroxiredoxin-2, glutathione peroxidase, GSH:GSSG ratios). Interestingly, exogenous addition to RBCs of reactive species that are involved in vascular inflammation demonstrated a role for the β93Cys in hydrogen peroxide and chloramine consumption. To simulate oxidative stress and inflammation in vivo, mice were challenged with lipopolysaccharide (LPS). Notably, LPS induced a greater degree of hypotension and lung injury in B93A versus B93C mice, which was associated with greater formation of RBC reactive species and accumulation of DMPO-reactive epitopes in the lung. These data suggest that the β93Cys is an important effector within the RBC antioxidant network, contributing to the modulation of tissue injury during vascular inflammation.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Dario A
authors.initials: DA
authors.lastname: Vitturi
authors.forename: Chiao-Wang
authors.initials: CW
authors.lastname: Sun
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Harper
authors.forename: Bessy
authors.initials: B
authors.lastname: Thrash-Williams
authors.forename: Nadiezhda
authors.initials: N
authors.lastname: Cantu-Medellin
authors.forename: Balu K
authors.initials: BK
authors.lastname: Chacko
authors.forename: Ning
authors.initials: N
authors.lastname: Peng
authors.forename: Yanying
authors.initials: Y
authors.lastname: Dai
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wyss
authors.forename: Tim
authors.initials: T
authors.lastname: Townes
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D006454:Hemoglobins; D008070:Lipopolysaccharides; D006861:Hydrogen Peroxide; D003545:Cysteine