Oxidative stress-associated shape transformation and membrane proteome remodeling in erythrocytes of end stage renal disease patients on hemodialysis

Antonelou, Marianna H.; Kriebardis, Anastasios G.; Velentzas, Athanassios D.; Kokkalis, Apostolos C.; Georgakopoulou, Sofia-Christina; Papassideri, Issidora S.

doi:10.1016/j.jprot.2011.04.009

Cited by 40 publications

(52 citation statements)

References 47 publications

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“…These solutions, however, do not completely protect the banked RBC as they undergo significant morphological and molecular changes during storage. These changes, collectively termed “RBC storage lesions”, can be catalyzed by oxidation, and include a gradual degradation of membrane proteins such as Band-3 [7]–[12]. Accelerated senescence due to oxidation is not limited to storage conditions as it may also be at play during the normal aging process in vivo .…”

Section: Introductionmentioning

confidence: 99%

Serotonin Is a Key Factor for Mouse Red Blood Cell Survival

et al. 2013

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Serotonin (5-HT) is a monoamine originally purified from blood as a vasoactive agent. In nonneuronal tissues, its presence is linked with the expression of tryptophan hydroxylase 1 (TPH1) that catalyzes the rate-limiting step of its synthesis. Targeted disruption in mice of the TPH1 gene results in very low levels of circulating 5-HT. Previous analysis of the TPH1 knockout (TPH1−/−) mouse revealed that they develop a phenotype of macrocytic anemia with a reduced half-life of their circulating red blood cells (RBC). In this study, to establish whether the observed reduced half-life of TPH1−/− RBC is an intrinsic or an extrinsic characteristic, we compared their survival to RBC isolated from wild-type mice. Both in vivo and in vitro data converge to demonstrate an extrinsic protective effect of 5-HT since presence of 5-HT in the RBC environment protects RBC from senescence. The protective effect played by 5-HT is not mediated through activation of a classical pharmacological pathway as no 5-HT receptors were detected on isolated RBC. Rather, 5-HT acts as an effective antioxidant since reduction of 5-HT circulating levels are associated with a decrease in the plasma antioxidant capacity. We further demonstrate a link between oxidation and the removal of damaged RBC following transfusion, as supplementation with 5-HT improves RBC post-transfusion survival in a mouse model of blood banking.

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Section: Introductionmentioning

confidence: 99%

Serotonin Is a Key Factor for Mouse Red Blood Cell Survival

et al. 2013

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“…4,10 Furthermore, ROS promote changes in the protein expression profile, which may modify cellular function. [11][12][13][14][15] High levels of oxidative stress induce cell death in several cell types. Moreover, it has been reported that increases in oxidative stress provoke cellular malignant transformation in the context of cancer.…”

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confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

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During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

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“…Morphological changes induced by A23187 in the presence of Ca 2+ were associated with cell shrinkage, one of the characteristic features of apoptosis that distinguishes this active and regulated self-destruction process from the passive and chaotic event of necrosis induced by plasma membrane damage (Bratosin et al, 2001). On the other hand, stomatocytes were the main morphological cell transformation associated to in vitro (Vota et al, 2010) and in vivo (Richards et al, 2007;Antonelou et al, 2011) oxidative stress (Figure 1). Fig.…”

Section: Erythrocyte Morphologymentioning

confidence: 97%

“…The intrinsic oxidative stimuli related to the uremic state were closely associated with membrane cytoskeleton instability, loss of surface area through vesiculation, and transformation of normal discocytes. The observed alterations might contribute to premature erythrocyte death and to the progression of anemia (Antonelou et al, 2011). Under normal conditions, red blood cells are continuously exposed to ROS from both internal and external sources.…”

Section: In Vivo Erythrocyte Death and Possible Preventionmentioning

confidence: 99%