Hemoglobin Redox Reactions and Red Blood Cell Aging

Abstract

Significance: The physiological mechanism(s) for recognition and removal of red blood cells (RBCs) from circulation after 120 days of its lifespan is not fully understood. Many of the processes thought to be associated with the removal of RBCs involve oxidative stress. We have focused on hemoglobin (Hb) redox reactions, which is the major source of RBC oxidative stress. Recent Advances: The importance of Hb redox reactions have been shown to originate in large parts from the continuous slow autoxidation of Hb producing superoxide and its dramatic increase under hypoxic conditions. In addition, oxidative stress has been shown to be associated with redox reactions that originate from Hb reactions with nitrite and nitric oxide (NO) and the resultant formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation. Critical Issues: The interaction of Hb, particularly under hypoxic conditions with band 3 of the RBC membrane is critical for the generating the RBC membrane changes that trigger the removal of cells from circulation. These changes include exposure of antigenic sites, increased calcium leakage into the RBC, and the resultant leakage of potassium out of the RBC causing cell shrinkage and impaired deformability. Future Directions: The need to understand the oxidative damage to specific membrane proteins that result from redox reactions occurring when Hb is bound to the membrane. Proteomic studies that can pinpoint the specific proteins damaged under different conditions will help elucidate the cellular aging processes that result in cells being removed from circulation. Antioxid. Redox Signal. 18, 2274-2283.

Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc

“…Our results corroborated with the findings of Ojezele and Abatan (2009), who reported a reduction in RBC and Hb in MD treated group, which can be attributed to intravascular haemolysis, anemia, or to haemopoeisis depression. On the other hand, the Hb is found to be a major source of radical production when it interacts with redox xenobiotics (French et al, 1978;Rifkind and Nagababu, 2013). Liver is the target organ of OPs toxicity (Mazumder, 2005), and the leakage of hepatic enzymes such as ALT, AST and ALP are commonly used as an indirect biochemical index of hepatocellular injury (Klaassen and Watkin, 1984).…”

Upregulation and Mitochondrial Sequestration of Hemoglobin Occur in Circulating Leukocytes during Critical Illness, Conferring a Cytoprotective Phenotype

“…Although hemoglobin is best known for its role as an oxygen carrier in erythrocytes, many biological functions of hemoglobin predate the evolution of the circulatory system and are used to modulate various redox functions and interactions with gaseous transmitters such as nitric oxide (NO) and hydrogen sulfide (H 2 S) (1)(2)(3)(4)(5). For instance, clams living in H 2 S-rich waters upregulate intracellular hemoglobin levels as a protective mechanism against H 2 S toxicity (5).…”

Markers of Oxidative Stress in Senescent Erythrocytes Obtained from Young and Old Age Rats

“…11 Increased accumulation of oxidized and denatured proteins, particularly hemoglobin, is also documented. 12 Studies have shown that erythrocyte aging in vivo is accompanied by a reduction in sodium-potassium adenosine triphosphatase (Na/K-ATPase), 13 Gardos channel, 14 and calcium (Ca 2 + )-ATPase with a concomitant significant increase in intracellular calcium. 15 Additionally, metabolic and functional changes have been observed for young and old erythrocytes kept outside the blood circulation.…”