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Review
. 2017 Feb 11;18(2):387.
doi: 10.3390/ijms18020387.

"VSports在线直播" Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion

Giona Sonego  1 , Mélanie Abonnenc  2 , Jean-Daniel Tissot  3   4 , Michel Prudent  5 , Niels Lion  6   7
Affiliations
Review

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

Giona Sonego et al. Int J Mol Sci. .

Abstract

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 VSports手机版. 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. .

Keywords: activation; aggregation; blood products; phosphorylation; platelet function; platelets; reactive oxygen species; redox cysteine; transfusion V体育安卓版. .

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Conflict of interest statement

Niels Lion received a conference honorarium on two occasions from Cerus, the provider of the INTERCEPT Blood System. Jean-Daniel Tissot received an honorarium from TerumoBCT (European customer panel). The other authors have disclosed no conflict of interest V体育ios版.

Figures

Figure 1
Figure 1
The steps in platelet activation and aggregation in thrombus formation after wounding. Damage to the epithelial wall of a vein exposes vWF and collagen. Receptors on platelets, such as glycoprotein Ib-IX (GP-Ib-IX), αIIbβ3, and glycoprotein VI (GPVI), reversibly bind to newly-exposed proteins (1). This induces internal signaling, leading to platelet activation (2). Platelets undergo degranulation (3) and secrete chemokines, including ADP, serotonin, ions like Ca2+, and other molecules that recruit additional platelets (4). Once activated platelets are bound on the endothelial wall, they progressively and definitively stick on the vein, changing their shape (5). Activated platelets form crosslinks via fibrinogen bridges between αIIbβ3 proteins, forming the thrombus (6).
Figure 2
Figure 2
The role of NOX (NOX1 and/or NOX2) in thrombus formation via ROS production. Increased intracellular ROS production enhances (+) redox internal signaling. ROS potentiate the PLCγ/PKC/MAPKp38 signaling cascade, thereby inducing phospholipase A2 (PLA2) activation via (arrows) phosphorylation. PLA2 catalyzes the hydrolysis of the phospholipid sn2-acyl bond at the membrane, releasing arachidonic acid (AA) into the cytoplasm. AA can either be converted by COX1 into prostaglandin G2 (PGG2), an intermediate in the synthesis of thromboxane A2 (TxA2), or it can be oxidized by peroxides to form F2 isoprostane (F2-IsoP). Both can bind the prostanoid TP receptor during thrombosis/hemostasis. O2−· can be converted into the more membrane permeable H2O2 by superoxide dismutase (SOD). H2O2 acts as a second messenger in various cellular signaling pathways, and it also induces Ca2+ mobilization. Ca2+ mobilization precede the glycoprotein GPIIb/IIIa (or αIIbβ3) affinity modulation to fibrinogen binding. Alternatively, O2−· reacts with NO, leading to reactive nitrogen species such as ONOO−.
Figure 3
Figure 3
Ca2+ mobilization upon stimulation with collagen agonists. Collagen induces the assembly of NOX complexes at the membrane. O2−· is converted by SOD into the thiol effector and membrane permeable (black arrow) H2O2, which reversibly switches off the SHP-2 phosphatase SHP-2 cysteine oxidation inhibits its phosphatase function (black T bars) and results in enhanced (red arrows) kinases Syk, Vav1, and Btk phosphorylation, essential for the activation of membrane complexes such as PLCγ-2 and LAT and inducing IP3 release in the cytosol. IP3 acts on the calcium channel, mobilizing Ca2+ (yellow arrow). Adapted from reference [31], courtesy of Tong-Shin Chang.
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References

    1. Garraud O. Editorial: Platelets as immune cells in physiology and immunopathology. Front. Immunol. 2015;6:274. doi: 10.3389/fimmu.2015.00274. - DOI - PMC - PubMed
    1. Rondina M.T., Weyrich A.S., Zimmerman G.A. Platelets as cellular effectors of inflammation in vascular diseases. Circ. Res. 2013;112:1506–1519. doi: 10.1161/CIRCRESAHA.113.300512. - V体育官网入口 - DOI - PMC - PubMed
    1. Holbro A., Infanti L., Sigle J., Buser A. Platelet transfusion: Basic aspects. Swiss Med. Wkly. 2013;143:13885. doi: 10.4414/smw.2013.13885. - DOI - PubMed
    1. Hoffmeister K.M., Felbinger T.W., Falet H., Denis C.V., Bergmeier W., Mayadas T.N., von Andrian U.H., Wagner D.D., Stossel T.P., Hartwig J.H. The clearance mechanism of chilled blood platelets. Cell. 2003;112:87–97. doi: 10.1016/S0092-8674(02)01253-9. - DOI - PubMed
    1. Salunkhe V., van der Meer P.F., de Korte D., Seghatchian J., Gutiérrez L. Development of blood transfusion product pathogen reduction treatments: A review of methods, current applications and demands. Transfus. Apher. Sci. 2015;52:19–34. doi: 10.1016/j.transci.2014.12.016. - DOI - PubMed

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