PubMed · 4189951
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J G White. 1970. The interplatelet zone.. https://pubmed.ncbi.nlm.nih.gov/4189951/
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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.
Ca(2+) release from internal stores as a result of activation of phospholipase C or inhibition of the endoplasmic reticulum pump is accompanied by Ca(2+) influx from the extracellular space. Measurement of intracellular calcium concentration and fluorescence quenching in Fura2-loaded cells showed that platelets preincubated in lithium have significantly higher basal, but lower agonist-stimulated influx of Mn(2+) (acting as a surrogate of Ca(2+) influx), than platelets reloaded with calcium in a normal sodium medium. There is no difference in the basal entry of divalent ion in platelets preincubated in sodium, lithium, or N-methyl glucamine in the absence of calcium. In platelets preincubated in lithium there is a higher basal Mn(2+) entry without further increase upon store depletion by thapsigargin. In contrast, a significant increase in the divalent ion influx was found in sodium or N-methyl glucamine attributable to the opening of channels sensitive to store depletion. In the absence of extracellular calcium, the empty store opens channels and Li(+) did not have additional effect on channels that are already open. The refilling of the stores with Ca(2+) suppresses Mn(2+) entry after sodium or NMG preincubation, but not after lithium preincubation. We propose that lithium induces a calcium influx throughout store-operated channels. This hypothesis may explain the lack of additivity, in cell preincubated in lithium, of basal entry and thapsigargin-triggered entry of calcium.
Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-1) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with alpha-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P<0.01) that could be inhibited by interleukin-1 (IL-1) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappaB (NF-kappaB) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-1 mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and kappaB-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-1) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.