Abstract
α1-microglobulin (A1M) is a small protein present in vertebrates including humans. It has several physiologically relevant properties, including binding of heme and radicals as well as enzymatic reduction, that are used in the protection of cells and tissue. Research has revealed that A1M can ameliorate heme and ROS-induced injuries in cell cultures, organs, explants and animal models. Recently, it was shown that A1M could reduce hemolysis in vitro, observed with several different types of insults and sources of RBCs. In addition, in a recently published study, it was observed that mice lacking A1M (A1M-KO) developed a macrocytic anemia phenotype. Altogether, this suggests that A1M may have a role in RBC development, stability and turnover. This opens up the possibility of utilizing A1M for therapeutic purposes in pathological conditions involving erythropoietic and hemolytic abnormalities. Here, we provide an overview of A1M and its potential therapeutic effect in the context of the following erythropoietic and hemolytic conditions: Diamond-Blackfan anemia (DBA), 5q-minus myelodysplastic syndrome (5q-MDS), blood transfusions (including storage), intraventricular hemorrhage (IVH), preeclampsia (PE) and atherosclerosis.
Highlights
Oxidative stress is defined as an imbalance between the production of oxidants and reactive oxygen/nitrogen species (ROS/RNS), including free radicals, and the antioxidant defense capacity, leading to molecular damage and/or disrupted redox signaling [1]
Moderate amounts of leaked red blood cells (RBCs) components are balanced by an arsenal of protective proteins, a network of endogenous antioxidants, e.g., haptoglobin, hemopexin, heme oxygenases and α1-microglobulin (A1M) [4]
Recombinant human A1M protected murine RBCs from hemolysis in vitro, suggesting that the effect is not species-specific. These results suggest that the addition of A1M may be beneficial in stabilizing RBCs and reducing hemolysis regardless of hemolytic insult
Summary
Oxidative stress is defined as an imbalance between the production of oxidants and reactive oxygen/nitrogen species (ROS/RNS), including free radicals, and the antioxidant defense capacity, leading to molecular damage and/or disrupted redox signaling [1]. Our group published data showing that recombinant human A1M, a therapeutic candidate that has been shown to be functionally equivalent to endogenous A1M and that can be produced in large scale, can protect RBCs in vitro and that mice lacking A1M had an altered blood composition [8]. These data suggest that A1M may have a role in RBC development and stability. In light of these new findings, we discuss here the physiological consequences of such a role of A1M in RBC homeostasis by presenting an overview of A1M followed by a discussion of pathological erythropoietic and hemolytic conditions where A1M may constitute a therapeutic opportunity
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