Oxygen removal during pathogen inactivation with riboflavin and <scp>UV</scp> light preserves protein function in plasma for transfusion

Feys, Hendrik B.; Aelst, Britt Van; Devreese, Katrien; Devloo, Rosalie; Coene, J.; Vandekerckhove, Philippe; Compernolle, Veerle

doi:10.1111/vox.12106

Cited by 19 publications

(22 citation statements)

References 35 publications

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“…19,33 Previously, several studies have reported that RF and UV light can trigger intracellular generation of ROS in PLTs modulating signaling pathways and causing oxidative damage of macromolecules. 20,21,34 In this study, we also show that the RF/UV treatment generated intracellular H 2 O 2 in apheresis PCs throughout storage, which might contribute to the depolarization of the DW m further contributing to apoptosis development.…”

Section: Discussionsupporting

confidence: 56%

“…Accumulating evidence demonstrates that PI-treated PLTs share highly similar behaviors with PLTs stimulated by physiologic activators, including PLT activation, degranulation, and development of apoptosis, leading to the conclusion that these processes have the same signaling mechanism. Lopez and coworkers 30 reported that thrombin induces translocation of Bax, Bak, and active Bid to MT resulting in cyto c release and subsequent loss 20,21,34 In this study, we also show that the RF/UV treatment generated intracellular H 2 O 2 in apheresis PCs throughout storage, which might contribute to the depolarization of the DW m further contributing to apoptosis development. …”

supporting

confidence: 66%

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p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

et al. 2017

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BACKGROUND: Biochemical analyses of mechanisms triggered in platelets (PLTs) upon pathogen inactivation (PI) are crucial to further understand the impact of PI on PLT functionality and, subsequently, quality. STUDY DESIGN AND METHODS: PLT concentrates(PCs) were split into four small illumination bags: 1) untreated control, 2) treated with riboflavin and ultraviolet light (RF/UV), and spiked with 3) solvent control dimethyl sulfoxide and 4) p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 before RF/UV treatment. Flow cytometry was used to monitor PLT mitochondrial potential (DW m ); generation of intracellular reactive oxygen species (ROS); and release of microvesicles (MVs), mitochondria (MT), and MVs containing MT (MVs/ MT). Quantitative polymerase chain reaction (qPCR) was used to quantify extracellular mitochondrial DNA (mtDNA). Translocation of selected mitochondrial proteins was analyzed in subcellular fractions by immunoblot.RESULTS: RF/UV treatment triggered an increased mitochondrial translocation of both Bax and Bid (p < 0.05, Day 7) and cytochrome c release (p < 0.01, Day 7), loss of DW m (p < 0.05, Day 5 and Day 7), and ROS generation (p < 0.01, Day 5 and Day 7) in PCs compared to the untreated control during storage. These PI-triggered changes were inhibited by SB203580 (p < 0.05). The release of MVs, MT, and MVs/MT was increased upon the RF/UV treatment during storage (p < 0.05) and, with the exception of MT, the release was decreased by the inhibitor (p < 0.05). qPCR analysis showed that RF/UV does not trigger mtDNA release during storage. CONCLUSION:These findings further our understanding of mechanisms in PLTs initiated by the RF/UV treatment, demonstrating that this treatment induces p38 MAPK-dependent mitochondrial signaling and MV release in apheresis PCs. R iboflavin and ultraviolet light (RF/UV) treatment is one of several pathogen inactivation (PI) technologies currently available.1 These treatments aim to target the replication and/or proliferation mechanism of pathogens and to destroy residual white blood cells (WBCs) to improve the safety of blood 14,15,25 The aim of this study was to evaluate the effects of RF/UV treatment on PLT mitochondrial function and signaling, including the recently discovered release of MT by PLTs, and to determine whether p38 is involved in the modulation of these mechanisms. MATERIALS AND METHODS MaterialsCommon chemicals were purchased from Sigma-Aldrich or Fisher Scientific. SB203580, a p38 MAPK inhibitor, was purchased from Santa Cruz Biotechnology. Apheresis PC preparationThis study was approved by the research ethics board of Canadian Blood Services and informed consent was obtained from all healthy volunteers before blood donation. Phlebotomy and plateletpheresis were carried out by the NetCAD development laboratory of Canadian Blood Services (Vancouver, Canada) using a Trima Accel (TerumoBCT). RF/UV treatment and inhibitor studyThe SB inhibitor stock solution in dimethyl sulfoxide (DMSO) was diluted in phosphate-buffered saline (PBS) and...

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Section: Discussionsupporting

confidence: 56%

supporting

confidence: 66%

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

et al. 2017

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“…Hydrogen peroxide is capable of causing oxidative damage to platelet proteins [41], and a recent study demonstrates that riboflavin/UV treatment of platelets induces oxidative modification of selected peptides, such as fibronectin [42], and Mirasol treatment of plasma increases protein carbonylation [15]. Protein carbonylation is widely used as a marker of protein oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…Further, Mirasol treatment of plasma has recently been shown to result in oxidative damage of key plasma proteins [15]. As platelets generate ROS during activation [16,17] and ROS are capable of selectively modulating platelet activation [18,19], it is imperative to understand the role of Mirasol treatment in this context to ensure a complete understanding of the toxicological profile of this component [20].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation

Johnson¹,

Marks²

2015

Transfus Med Hemother

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Background: Pathogen inactivation (PI) technologies for platelets aim to improve transfusion safety by preventing the replication of contaminating pathogens. However, as a consequence of treatment, aspects of the platelet storage lesion are amplified. Mirasol treatment also affects platelet signal transduction and apoptotic protein expression. The aim of this study was to examine the effect of Mirasol treatment on the generation of reactive oxygen species (ROS) and subsequent oxidative stress. Methods: Pooled platelet concentrates were prepared in platelet-additive solution (70% SSP+ / 30% plasma). ABO-matched platelets were pooled and split, and treated with the Mirasol system (TerumoBCT) or left untreated as a control. Platelet samples were tested on day 1, 5, and 7 post-collection. Results: Mirasol-treated platelets had increased formation of ROS by day 5 of storage. Oxidative damage, in the form of protein carbonylation, was higher in Mirasol-treated platelets, whilst no effect on nitrotyrosine formation or lipid peroxidation was detected. The NF-κB signaling pathway was also activated in Mirasol-treated platelets, with increased expression and phosphorylation of NF-κB p65 and IκBa. Conclusion: These data demonstrate that Mirasol-treated platelets produce more ROS and display protein alterations consistent with oxidative damage.

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“…Der Riboflavinabbau ist zeitabhängig [98]. Umfangreiche toxikologische Untersuchungen sind unternommen worden, um die Sicherheit der mit MIRASOL® behandelten Blutprodukte nachzuweisen (Übersicht in [69,70] [17,115,116]. Dennoch finden sich nach einer PI mit MIRASOL® nur geringe Veränderungen am Gesamtproteom [67].…”

Section: Unerwünschte Effekte Der Pathogeninaktivierung Mit Mirasol®unclassified

Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate

2018

Bundesgesundheitsbl

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Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion

Abstract: RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.

Cited by 19 publications

References 35 publications

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation

Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate

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Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion

Abstract: RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.

Cited by 19 publications

References 35 publications

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-&#954;B Activation

Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate

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Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System Modulates Platelet Oxidative Stress and NF-κB Activation