Response: Hemolysis is a primary and physiologically relevant ATP release mechanism in human erythrocytes

Sikora, Jacek; Orlov, Sergei N.; Furuya, Kishio; Grygorczyk, Ryszard

doi:10.1182/blood-2015-01-622159

Cited by 10 publications

(8 citation statements)

References 12 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, a crosstalk of nitrite export mechanisms and ATP release in hypoxic vasodilation was also reported ( 29 ). These data were recently challenged in a methodological article by a significant correlation between ATP release and hemolysis (measured as Hb concentration in the supernatant), leading to a still ongoing discussion on the significance of RBC-mediated ATP release ( 98 , 167 ).…”

Section: Rbcs and No Metabolismmentioning

confidence: 99%

Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

Kuhn

Diederich

Keller

et al. 2017

Antioxidants & Redox Signaling

339

250

View full text Add to dashboard Cite

Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified.Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia.Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far.Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742.

show abstract

Section: Rbcs and No Metabolismmentioning

confidence: 99%

Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

Kuhn

Diederich

Keller

et al. 2017

Antioxidants & Redox Signaling

339

250

View full text Add to dashboard Cite

show abstract

“…However, we were not able to demonstrate changes of stimulated ATP release in our in vitro system, in which we incubated RBCs with LA or ALA for 4–8 h. Handling and media conditions play a critical role in analysing a controlled ATP release from intact RBC. It was discussed that haemolysis is the primary release mechanism for ATP [48]. In accordance with other studies [49,50,51], we used an isotonic medium for the preparation of RBC and checked the osmolarity of the media as well as the concentration of free haemoglobin in our RBC preparations.…”

Section: Discussionmentioning

confidence: 80%

Dietary Fatty Acids Affect Red Blood Cell Membrane Composition and Red Blood Cell ATP Release in Dairy Cows

Revskij

Haubold

Viergutz

et al. 2019

IJMS

View full text Add to dashboard Cite

Diets of dairy cows are often based on maize silage (MS), delivering lower amounts of n-3 fatty acids (FA) compared to grass silage-based diets. The fatty acid composition of the cell membrane can affect the cell function. We evaluated the effects of an MS-based diet on bovine red blood cell (RBC) membrane FA composition and dietary effects on controlled ATP release of RBC. In trial 1, German Holstein cows were fed an MS-based total mixed ration for 24 weeks. The FA composition of RBC membranes from repeatedly taken blood samples was analysed in addition to the abundance of the RBC membrane protein flotillin-1, which is involved in, for example, cell signalling. In trial 2, four rumen fistulated MS-fed cows were abomasally infused in a 4 × 4 Latin square model with three successively increasing lipid dosages (coconut oil, linseed–safflower oil mix (EFA; rich in n-3 FA), Lutalin®, providing conjugated linoleic acids (CLA) or the combination of the supplements, EFA + CLA) for six weeks, followed by a three-week washout period. In trial 2, we analysed RBC ATP release, flotillin-1, and the membrane protein abundance of pannexin-1, which is involved in ATP release as the last part of a signalling cascade. In trial 1, the total amount of n-3 FA in RBC membranes decreased and the flotillin-1 abundance increased over time. In trial 2, the RBC n-3 FA amount was higher after the six-week infusion period of EFA or EFA + CLA. Furthermore, depending on the dosage of FA, the ATP release from RBC increased. The abundance of flotillin-1 and pannexin-1 was not affected in trial 2. It is concluded that changes of the membrane FA composition influence the RBC function, leading to altered ATP release from intact bovine RBC.

show abstract

“…Although it has been also considered to be a potential factor contributing to stimulated ATP release in most previous in vitro investigations, its actual involvement has often not been assessed systematically. By paired measurements of ATP and free hemoglobin in each and every sample of human RBC supernatants Sikora et al found that basal and stimulated ATP release not only correlated tightly with extracellular hemoglobin, but matched the levels expected from cell lysis and independently determined cell ATP content (Sikora et al, 2014 , 2015 ). Unexpectedly, this was seen with all stimuli tested (hypotonic shock, shear stress, hypoxia) strongly indicating that, for each stimulus, the only source of extracellular ATP was cell lysis (Sikora et al, 2014 ; Luneva et al, 2016 ).…”

Section: Introductionmentioning

confidence: 95%

“…Surprisingly, stimulation of cAMP pathway had no effect on RBC ATP release, which remained at the basal level observed with unstimulated cells. The report triggered a significant debate in the field with opposing views presented by Kirby et al ( 2015 ) and Sikora et al ( 2015 ). Absence of cAMP-regulated ATP release was recently confirmed by Keller et al who also showed using Panex1 −/− mice model that Panex1 has no role in exercise performance, challenging assumptions about Panex1 role in ATP-dependent blood perfusion to exercising skeletal muscle (Keller et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Hypoxia on Erythrocyte Membrane Properties—Implications for Intravascular Hemolysis and Purinergic Control of Blood Flow

Grygorczyk

Orlov

2017

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

Intravascular hemolysis occurs in hereditary, acquired, and iatrogenic hemolytic conditions but it could be also a normal physiological process contributing to intercellular signaling. New evidence suggests that intravascular hemolysis and the associated release of adenosine triphosphate (ATP) may be an important mechanism for in vivo local purinergic signaling and blood flow regulation during exercise and hypoxia. However, the mechanisms that modulate hypoxia-induced RBC membrane fragility remain unclear. Here, we provide an overview of the role of RBC ATP release in the regulation of vascular tone and prevailing assumptions on the putative release mechanisms. We show importance of intravascular hemolysis as a source of ATP for local purinergic regulation of blood flow and discuss processes that regulate membrane propensity to rupture under stress and hypoxia.

show abstract

Response: Hemolysis is a primary and physiologically relevant ATP release mechanism in human erythrocytes

Cited by 10 publications

References 12 publications

Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

Dietary Fatty Acids Affect Red Blood Cell Membrane Composition and Red Blood Cell ATP Release in Dairy Cows

Effects of Hypoxia on Erythrocyte Membrane Properties—Implications for Intravascular Hemolysis and Purinergic Control of Blood Flow

Contact Info

Product

Resources

About