Metabolomics study of platelet concentrates photochemically treated with amotosalen and UVA light for pathogen inactivation

Jóhannsson, Freyr; Árnason, Níels Árni; Landrö, Ragna; Guðmundsson, Sveinn; Sigurjónsson, Ólafur E.; Rolfsson, Óttar

doi:10.1111/trf.15610

Cited by 5 publications

(5 citation statements)

References 56 publications

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“…A decrease in CCI with or without impact on PC consumption has been reported [1‒3]. This observation might be explained by an increase of PS expression, platelet activation, and GPIb shedding, as mentioned in Introduction [4‒17]. The activation of the MAPK pathway is in agreement with this phenotype, where p38 phosphorylation is induced by amotosalen/UVA treatment and related to PS expression and GPIb shedding that primes this receptor for cleavage.…”

Section: Discussionmentioning

confidence: 63%

“…Indeed, these photochemical or photo-treatments modify the phenotype and functions of platelets to different extents. Compared to untreated PCs, increased p-selectin expression (platelet activation), exposure of phosphatidylserine (marker of senescence), decrease in GPIb expression (von Willebrand receptor), activation of integrin αIIbβ3 (fibrinogen receptor), modulation of aggregation responses (function of agonists), and modification of metabolite levels have been reported [8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates

Muret,

Crettaz,

Alberio

et al. 2024

Transfus Med Hemother

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Background: Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level. Objectives: This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs. Method: A two-arm study setting was carried out to compare PIT (amotosalen/UVA) to untreated PCs, on day 1 post-donation. Based on a pool-and-split approach, 12 PCs were split into two groups (treated and untreated). Quantitative phosphoproteomics was performed using TMT technology to study the changes of phosphoproteins right after the PIT. Results: A total of 3,906 proteins and 7,334 phosphosites were identified, and 2,473 proteins and 2,214 phosphosites were observed in at least 5 to 6 replicates. Compared to untreated platelets, PIT platelets exhibited an upregulation of the phosphorylation effects, with 109 phosphosites identified with a higher than 2-fold change. Two pathways were clearly identified. The mitogen activated protein kinases (MAPKs) cascade, which triggers the granule secretion and the activation of the pS15 HSPB1. One of the shape change pathways was also observed with the inhibition of the Threonine 18 and Serine 19 phosphorylations on myosin light chain (MLC) protein after the amotosalen/UVA treatment. Conclusions: This work provides a deep insight into the impact of amotosalen/UVA treatment from a phosphoprotein viewpoint on resting platelets. Clear changes in phosphorylation of proteins belonging to different platelet pathways were quantified. This discovery corroborates previous findings and fills missing parts of the effect of photochemical treatments on platelets.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates

Muret,

Crettaz,

Alberio

et al. 2024

Transfus Med Hemother

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“…Possible causes are protein degradation caused by UV-light exposure [ 68 ] or incubation with the compound absorption device. Our group has shown that specific metabolite species show a significant concentration drop after PI processing, especially after the compound absorption phase [ 69 ]. The decrease in levels of specific proteins can be beneficial for patients, especially if these proteins have been implicated in transfusion reactions.…”

Section: Discussionmentioning

confidence: 99%

“…Hierarchical clustering was performed using Euclidean distance and Ward’s method. Principal components analysis (PCA), a dimensionality reduction technique used to preserve as much of the variance of data as possible in lower-dimensional output [ 69 ], was performed using R v3.5.1 (R Development Core Team).…”

Section: Methodsmentioning

confidence: 99%

Protein Concentrations in Stored Pooled Platelet Concentrates Treated with Pathogen Inactivation by Amotosalen Plus Ultraviolet a Illumination

et al. 2022

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Platelet granules contain a diverse group of proteins. Upon activation and during storage, platelets release a number of proteins into the circulation or supernatant of stored platelet concentrate (PC). The aim of this work was to investigate the effect of pathogen inactivation (PI) on a selection of proteins released in stored platelets. Materials and Methods: PCs in platelet additive solution (PAS) were produced from whole blood donations using the buffy coat (BC) method. PCs in the treatment arm were pathogen inactivated with amotosalen and UVA, while PCs in the second arm were used as an untreated platelet control. Concentrations of 36 proteins were monitored in the PCs during storage. Results: The majority of proteins increased in concentration over the storage period. In addition, 10 of the 29 proteins that showed change had significantly different concentrations between the PI treatment and the control at one or more timepoints. A subset of six proteins displayed a PI-related drop in concentration. Conclusions: PI has limited effect on protein concentration stored PC supernatant. The protein’s changes related to PI treatment with elevated concentration implicate accelerated Platelet storage lesion (PSL); in contrast, there are potential novel benefits to PI related decrease in protein concentration that need further investigation.

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“…Intra- and extracellular samples were analysed by hydrophilic interaction liquid chromatography [HILIC] coupled with time-of-flight (TOF) mass spectrometry (Synapt G2, Waters, UK) using a previously described method 23 . Each sample was measured both in positive and negative ionization mode.…”

Section: Methodsmentioning

confidence: 99%

The Anti-Proliferative Lichen-Compound Protolichesterinic Acid Inhibits Oxidative Phosphorylation and Is Processed via the Mercapturic Pathway in Cancer Cells

Jóhannsson

Cherek

et al. 2021

Planta Med

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The lichen compound protolichesterinic acid (PA) has an anti-proliferative effect against several cancer cell lines of different origin. This effect cannot be explained by the known inhibitory activity of PA against 5- and 12-lipoxygenases. The aim was therefore to search for mechanisms for the anti-proliferative activity of PA. Two cancer cell lines of different origin, both sensitive to anti-proliferative effects of PA, were selected for this study, T-47D from breast cancer and AsPC-1 from pancreatic cancer. Morphological changes were assessed by transmission electron microscopy, HPLC coupled with TOF spectrometry was used for metabolomics, mitochondrial function was measured using the Agilent Seahorse XFp Real-time ATP assay and glucose/lactate levels by radiometry. Levels of glutathione, NADP/NADPH and reactive oxygen species [ROS] were measured by luminescence. Following exposure to PA both cell lines showed structural changes in mitochondria that were in line with a measured reduction in oxidative phosphorylation and increased glycolysis. These changes were more marked in T-47D, which had poorer mitochondrial function at baseline. PA was processed and expelled from the cells via the mercapturic pathway, which consumes glutathione. Nevertheless, glutathione levels were increased after 24 hours of exposure to PA, implying enhanced synthesis. Redox balance was not much affected and ROS levels were not increased. We conclude that PA is metabolically processed and expelled from cells, leading indirectly to increased glutathione levels with minimal effects on redox balance. The most marked effect was on mitochondrial structure and metabolic function implying that effects of PA may depend on mitochondrial fitness.

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Metabolomics study of platelet concentrates photochemically treated with amotosalen and UVA light for pathogen inactivation

Cited by 5 publications

References 56 publications

Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates

Increase of Phosphoprotein Expressions in Amotosalen/UVA-Treated Platelet Concentrates

Protein Concentrations in Stored Pooled Platelet Concentrates Treated with Pathogen Inactivation by Amotosalen Plus Ultraviolet a Illumination

The Anti-Proliferative Lichen-Compound Protolichesterinic Acid Inhibits Oxidative Phosphorylation and Is Processed via the Mercapturic Pathway in Cancer Cells

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