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. Since this residue is present at concentrations more than two 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 positions, 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 RBC 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 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.

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

“…The presence of nitrite and NO will also foster the formation of SNO-Hb, in which the thiols on b93 cysteine are S-nitrosated. SNO Hb formation has been shown (198) to play a role in limiting oxidative stress and erythrocyte membrane damage by further supporting the concept that NO in many or all of its bioactive forms can function to maintain RBC homeostasis in the presence of oxidative stress. Furthermore, SNO Hb formation has also been shown to be a significant contributor to the mechanism for hypoxic vasodilation (212).…”

“…This oxidation is significant, in that the reduced state of these thiols plays a key role in protecting against oxidative stress (198). It is when the b93 Cys are oxidized that Hb alterations occur, including Hb dimer/hemichrome formation, which can disrupt the functional Band 3 protein complex under conditions of oxidative stress (110).…”

Influence of freezing down to 77.15 K on structure and antioxidant power of some proteins

“…Hemoglobin molecule has also free SH-groups of Cys [16]. Experimental data have shown the increasing of the level of hemoglobin light scattering, being the most pronounced after rapid freezing (Fig.…”

The ameliorative effect ofCetraria islandicaagainst diabetes-induced genetic and oxidative damage in human blood

“…Recent studies suggested a strong antioxidant effect of lichen extract that could ameliorate oxidative stress (Kosanic & Rankovic, 2011). The effects of antioxidants are pronounced in erythrocytes because these cells have increased amounts of hemoglobin and iron ions and consequently they are under higher oxidative stress (Vitturi et al, 2013). The results obtained in vitro suggest that the membrane fragility increases under oxidative stress conditions for the patient RBCs and the protection effect of antioxidants is due to their antioxidant properties (Moreira et al, 2011).…”