Advanced Glycation-Modified Human Serum Albumin Evokes Alterations in Membrane and Eryptosis in Erythrocytes

Abstract

Increased burden of advanced glycation end-products (AGEs) in case of hyperglycemic conditions leads to the development of retinopathy, nephropathy, and cardiovascular and neurological disorders such as Alzheimer's disease. AGEs are considered as pro-oxidants, and their accumulation increases the oxidative stress. The prolonged exposure to these AGEs is the fundamental cause of chronic oxidative stress. Abnormal morphology of red blood cells (RBCs) and excessive eryptosis has been observed in diabetes, glomerulonephritis, dyslipidemia, and obesity, but yet the contribution of extracellular AGEs remains undefined. In this study, we investigated the effect of AGEs on erythrocytes to determine their impact on the occurrence of different pathological forms of these blood cells. Specifically, carboxymethyllysine (CML), carboxyethyllysine (CEL), and Arg-pyrimidine (Arg-P) which have been reported to be the most pre-dominant AGEs formed under in vivo conditions were used in this study. Results suggested the eryptotic properties of CML, CEL, and Arg-P for RBCs, which were evident from the highly damaged cell membrane and occurrence of abnormal morphologies. Methylglyoxal-modified albumin showed more severe effects, which can be attributed to the high reactivity and pro-oxidant nature of glycation end products. These findings suggest the possible role of AGE-modified albumin towards the morphological changes in erythrocyte's membrane associated with diabetic conditions.

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

“…As a long-lived protein, RBC is prone for glycation. Glycation of RBC protein may alter RBC rheological property (e.g., aggregability or deformability) resulting in Hb bursts from RBC [41]. Serum free Hb or AGE-modified protein can be uptake through receptor-mediated endocytosis or phagocytosis and degrade by protease through endosomal-lysosomal system [42,43].…”

Clinical Impact of Hemorheology on Subclinical Myocardial Injury in Patients with Hypertension

“…Several pathways by which AGEs or their receptors influence myocardial injury have been reported [ 24 - 26 ]. Furthermore, basic studies have indicated that AGEs influence hemorheology by mechanisms such as platelet aggregation, leukocyte-endothelial interaction and morphological changes in the erythrocyte membrane [ 27 - 29 ]. Thus, the results of this and previous studies indicate that hemorheology and AGEs are associated not only on the volar side of the lower arm but also in small cardiac vessels, consequently leading to myocardial injury in patients with hypertension.…”

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

“…According to a previous study, a significant correlation was observed between deficiency of GPx as well as glutathione reductase and a low hemoglobin concentration, thus, implicating oxidative stress as a possible cause of anemia in T2DM patients . The anemia is prevalent in 14‐45% of the patients and may in part result from an abnormal morphology of the erythrocytes leading to enhanced eryptosis in DM . The anemia in DM can be not attributed to a decreased formation of erythrocytes as reticulocyte number in DM was increased, but rather to an increased destruction of the erythrocytes as PS‐exposure was significantly increased in the DM patients.…”