Protein translation occurs in platelet concentrates despite riboflavin/UV light pathogen inactivation treatment

Schubert, Peter; Culibrk, Brankica; Karwal, Simrath; Goodrich, Raymond P.; Devine, Dana V.

doi:10.1002/prca.201500139

Cited by 17 publications

(24 citation statements)

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“…This level of peptide overlap between two independent experiments lies in the range of technical replicates showing 35% to 60% repeatability and is additionally impacted by the donor‐to‐donor variability. To detect biologically significant alterations, we applied selection criteria of a fold change of protein level of either less than 0.5 or more than 1.5 . There were no marked membrane protein changes over storage in RBC Ctrl .…”

Section: Resultsmentioning

confidence: 99%

“…To detect biologically significant alterations, we applied selection criteria of a fold change of protein level of either less than 0.5 or more than 1.5. 32 There were no marked membrane protein changes over storage in RBC Ctrl . While alterations appeared variable and inconsistent for RBC HH over storage (RBC HH Days 5 and 42), RBC HH displayed a number of reproducible protein changes with respect to RBC Ctrl at baseline ( Table 2).…”

Section: Proteomic Analysis Of Rbc Hh and Rbc Ctrl Ghost Fractions Dumentioning

confidence: 89%

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Proteomic analysis of red blood cells from donors exhibiting high hemolysis demonstrates a reduction in membrane‐associated proteins involved in the oxidative response

2017

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BACKGROUND The development of hemolysis during ex vivo hypothermic storage is multifaceted. Standardization of collection and production processes is used to minimize variability in biologics manufacturing and to maximize product quality. However, the influence of various donor characteristics on product quality is often difficult to evaluate and to control. Using a proteomic approach, we aimed to decipher relevant donor characteristics that may predict red blood cell (RBC) quality during storage. STUDY DESIGN AND METHODS Ten healthy volunteer donors exhibiting repeated high hemolysis at outdate (>0.8%; RBCHH) and 10 age‐ and sex‐matched control donors (RBCCtrl) were studied. Common quality variables were measured on Days 5, 14, 21, 28, and 42 of storage. Protein profiles of hemoglobin‐depleted membrane fractions from RBCHH and RBCCtrl donors were analyzed using a quantitative proteomics approach based on iTRAQ (isobaric tags for relative and absolute quantitation). RESULTS Time‐dependent lesion development was apparent in both donor populations. RBCHH exhibited reduced 2,3‐bisphosphoglycerate levels (p < 0.001) and morphologic score (p < 0.001), but displayed elevated hemolysis level (p < 0.001), RBC‐derived microvesicle formation (p < 0.001), and mean corpuscular fragility (p < 0.001) compared to RBCCtrl, indicating notable differences at the membrane between the two donor populations. Proteomic findings revealed a significant reduction in the level of proteins involved in oxidative response pathways at early time points in RBCHH compared to that of RBCCtrl. CONCLUSION The recruitment of these candidate proteins might be part of a response mechanism altered in RBCHH donors and therefore may be useful as a donor screening tool.

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Section: Resultsmentioning

confidence: 99%

Section: Proteomic Analysis Of Rbc Hh and Rbc Ctrl Ghost Fractions Dumentioning

confidence: 89%

Proteomic analysis of red blood cells from donors exhibiting high hemolysis demonstrates a reduction in membrane‐associated proteins involved in the oxidative response

2017

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“…The increase in abundance of α‐tubulin in the urea‐soluble fraction of refrigerated PLTs was considerable and cannot be accounted for solely by protein migration from the cytosol. Previous studies have demonstrated that PLTs contain the necessary machinery for de novo protein synthesis, which can be activated by storage at room temperature and the use of pathogen inactivation systems . Thus, it is plausible that refrigeration may also trigger the activation of de novo protein synthesis facilitating α‐tubulin production, although further studies are required to demonstrate this.…”

Section: Discussionmentioning

confidence: 99%

Refrigerated storage of platelets initiates changes in platelet surface marker expression and localization of intracellular proteins

et al. 2016

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“…PITs have also been found to exacerbate platelet storage lesions [37]. Even though platelets are enucleated cells, the platelets remain capable of synthesizing some proteins [36,38,39,40]. Indeed, much attention has been focused on the platelet proteome, which involves more than 4000 proteins to date [41], in order to better define the impact of PITs on platelet function.…”

Section: Alterations and Oxidation Of Platelet Proteinsmentioning

confidence: 99%

Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion

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Abonnenc

Tissot

et al. 2017

IJMS

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Blood banks use pathogen inactivation (PI) technologies to increase the safety of platelet concentrates (PCs). The characteristics of PI-treated PCs slightly differ from those of untreated PCs, but the underlying reasons are not well understood. One possible cause is the generation of oxidative stress during the PI process. This is of great interest since reactive oxygen species (ROS) act as second messengers in platelet functions. Furthermore, there are links between protein oxidation and phosphorylation, another mechanism that is critical for cell regulation. Current research efforts focus on understanding the underlying mechanisms and identifying new target proteins. Proteomics technologies represent powerful tools for investigating signaling pathways involving ROS and post-translational modifications such as phosphorylation, while quantitative techniques enable the comparison of the platelet resting state versus the stimulated state. In particular, redox cysteine is a key player in platelet activation upon stimulation by different agonists. This review highlights the experiments that have provided insights into the roles of ROS in platelet function and the implications for platelet transfusion, and potentially in diseases such as inflammation and platelet hyperactivity. The review also describes the implication of redox mechanism in platelet storage considerations.

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Protein translation occurs in platelet concentrates despite riboflavin/UV light pathogen inactivation treatment

Abstract: This study demonstrates for the first time that platelets can synthesize proteins despite the riboflavin and UV treatment and suggests that platelets may possess a mechanism to protect their mRNA from damage by the PI treatment.

Cited by 17 publications

References 40 publications

Proteomic analysis of red blood cells from donors exhibiting high hemolysis demonstrates a reduction in membrane‐associated proteins involved in the oxidative response

Proteomic analysis of red blood cells from donors exhibiting high hemolysis demonstrates a reduction in membrane‐associated proteins involved in the oxidative response

Refrigerated storage of platelets initiates changes in platelet surface marker expression and localization of intracellular proteins

Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion

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