PubMed · 10613677
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C P Hayward. 1999. Platelet multimerin and its proteolytic processing.. https://pubmed.ncbi.nlm.nih.gov/10613677/
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OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.
We have investigated the effects of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus formation under flow conditions. We demonstrate herein that tetramethylpyrazine inhibits shear-induced platelet aggregation under relatively high shear rate of 10,800 s(-1) with modest inhibition of those occurring under relatively low shear rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also demonstrate that platelet activation induced by shearing in the absence of exogenous platelet-activating agents such as ADP as evidenced by P-selectin surface expression and microparticle release detected by quantitative flow cytometry was also inhibited by tetramethylpyrazine. Moreover, we also demonstrate platelet thrombus formation on the collagen and von Willebrand factor (vWF) surface at high shear rates without significant influences on those occurring under relatively low shear rates. Because platelet thrombus formation occurring under high shear rates is known to be mediated by the vWF interaction with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated process of platelet thrombus formation. Our findings, indicating the unique antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the platelet thrombus formation under high shear rates, provide good reasons for developing chemical analogs having biological functions similar to or more potent than those of tetramethylpyrazine as antiplatelet agents having unique biological functions.
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