Suicidal erythrocyte death in end-stage renal disease

Abstract

Anemia in uremia results in part from eryptosis, the suicidal erythrocyte death. Eryptosis in uremia is triggered in part by a dialyzable plasma component. Eryptosis in uremia is further triggered by dialysis procedure. Eryptosis in uremia is in part due to increased cytosolic Ca(2+) concentration. Eryptosis in uremia is further due to oxidative stress and ceramide formation.

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

“…Patients with ESRD invariably suffer from anemia, which is considered to result in large part from impaired renal EPO and subsequent decrease in erythropoiesis, and to a lesser extent from accelerated eryptosis [3].…”

“…In contrast, RBCs from patients with end-stage renal disease (ESRD) show a reduced life span, changes in shape, and decreased deformability [2]. Although anemia in ESRD results mainly from erythropoietin and iron deficiency, these metabolic changes, associated to RBC senescence and aminophospholipid phosphatidylserine (PS) externalization, can accelerate clearance of circulating erythrocytes because of premature suicidal erythrocyte death or eryptosis characterized by PS exposure at the erythrocyte surface [3]. RBCs play an important role in the balance between generation and scavenging of nitric oxide (NO), which is a key regulator of vascular homeostasis [4].…”

Stimulation of Suicidal Erythrocyte Death by Naphthazarin

“…Naphthazarin sensitizes breast cancer cells to the pro-apoptotic effect of radiation [6]. Naphthazarin is effective by various cellular mechanisms including oxidative stress [7,8] [13,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and accelerated eryptosis contributes to the pathophysiology of several clinical conditions, such as iron deficiency, phosphate depletion, malignancy, metabolic syndrome, diabetes, hepatic and renal insufficiency, dehydration, hyperphosphataemia, haemolytic uraemic syndrome, sepsis, malaria, sickle cell disease, thalassaemia and Wilson's disease [13,[34][35][36].The present study explored whether naphthazarin is able to trigger suicidal death of erythrocytes, that is cells devoid of mitochondria and nuclei, key organelles in the execution of apoptosis. To this end, erythrocytes drawn from healthy volunteers were treated with naphthazarin, and phosphatidylserine surface abundance, cell volume, [Ca 2+ ] i , oxidative stress and ceramide abundance were determined.…”

“…Eryptosis could further be triggered by the activation of casein kinase 1a [13], Janus-activated kinase JAK3 [13], protein kinase C [13] or p38 kinase [13], and by inhibition of AMP-activated kinase AMPK [13], cGMP-dependent protein kinase [13], PAK2 kinase [13] or sorafenib/sunitinib-sensitive kinases [13]. Eryptosis may be elicited by a wide variety of chemicals [13,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and accelerated eryptosis contributes to the pathophysiology of several clinical conditions, such as iron deficiency, phosphate depletion, malignancy, metabolic syndrome, diabetes, hepatic and renal insufficiency, dehydration, hyperphosphataemia, haemolytic uraemic syndrome, sepsis, malaria, sickle cell disease, thalassaemia and Wilson's disease [13,[34][35][36].…”

Stimulation of Suicidal Erythrocyte Death by Sulforaphane

“…Eryptosis is elicited by a wide variety of xenobiotics [13,, including tannic acid [48], honokiol [62], gossypol [46], gambogic acid [63], tanshinone II A [47], apigenin [64], ursolic acid [65], thymoquinone [66], oridonin [67] and a-lipoic acid [14]. Moreover, eryptosis is accelerated in a wide variety of clinical conditions [11,68], including sepsis [69], fever [16], malaria [29,[70][71][72][73], sickle cell disease [43,[74][75][76][77][78][79][80], Wilson's disease [81], iron deficiency [82], malignancy [83], metabolic syndrome [44], diabetes [30], renal insufficiency [39,84,85], haemolytic uremic syndrome [86], hyperphosphataemia [87] and phosphate depletion [68].…”