Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

Liu, Yue; Yin, Hui-jun; Chen, Ke-ji

doi:10.1007/s11427-013-4551-8

Cited by 23 publications

(21 citation statements)

References 19 publications

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“…The rapid development of computational analyses and systems modeling approaches provides rich and substantial content of “biological networks”, and generates a new view of the life sciences and medical research [19]. Recently, the robustness of multiple systems biology platforms has enabled the discovery of underlying molecular mechanisms and connections between drugs and their targets (e.g., proteomics studies on activated blood circulation of Chinese medicinal herbs) [20]. Newly-developed algorithms and network-based computational models can integrate multilevel omics data and can optimize combinational regimens of drug development.…”

Section: Discussionmentioning

confidence: 99%

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology

et al. 2018

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BackgroundThe method of multiple targets overall control is increasingly used to predict the main active ingredient and potential target group of Chinese traditional medicines and to determine the mechanisms involved in their curative effects. Qingdai is the main traditional Chinese medicine used in the treatment of chronic myelogenous leukemia (CML), but the complex active ingredients and antitumor targets in treatment of CML have not been clearly defined in previous studies.Material/MethodsWe constructed a protein-protein interaction network diagram of CML with 638 nodes (proteins) and 1830 edges, based on the biological function of chronic myelocytic leukemia by use of Cytoscape, and we determined 19 key gene nodes in the CML molecule by network topological properties analysis in a data bank. Then, we used the Surflex-dock plugin in SYBYL7.3 docking and acquired the protein crystal structures of key genes involved in CML from the chemical composition of the traditional Chinese medicine Qingdai with key proteins in CML networks.ResultsAccording to the score and the spatial structure, the pharmacodynamically active ingredients of Qingdai are Isdirubin, Isoindigo, N-phenyl-2-naphthylamine, and Isatin, among which Isdirubin is the most important. We further screened the most effective activity key protein structures of CML to find the best pharmacodynamically active ingredients of Qingdai, according to the binding interactions of the inhibitors at the catalytic site performed in best docking combinations.ConclusionsThe results suggest that Isdirubin plays a role in resistance to CML by altering the expressions of PIK3CA, MYC, JAK2, and TP53 target proteins. Network pharmacology and molecular docking technology can be used to search for possible reactive molecules in traditional chinese medicines (TCM) and to elucidate their molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology

et al. 2018

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“…Meanwhile, the PubAngioGen is supported by National Consortium of GPCR of China; many experts in the field are involved in curating angiogenesis-related articles. While the amount of data entries is increasing daily, many exploring experiments are performed in our collaborators’ labs including high-throughput experiments like RNA-Seq ( 28 ) and LC MS/MS ( 29 ) to validate or extend our findings in PubAngioGen. Along with the accumulation of data, in the future, we will further extend and redefine angiogenesis-related pathways to help other researchers to better understand the mechanism of it.…”

Section: Discussionmentioning

confidence: 99%

PubAngioGen: a database and knowledge for angiogenesis and related diseases

Liu

Wang

et al. 2014

Nucleic Acids Research

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Angiogenesis is the process of generating new blood vessels based on existing ones, which is involved in many diseases including cancers, cardiovascular diseases and diabetes mellitus. Recently, great efforts have been made to explore the mechanisms of angiogenesis in various diseases and many angiogenic factors have been discovered as therapeutic targets in anti- or pro-angiogenic drug development. However, the resulted information is sparsely distributed and no systematical summarization has been made. In order to integrate these related results and facilitate the researches for the community, we conducted manual text-mining from published literature and built a database named as PubAngioGen (http://www.megabionet.org/aspd/). Our online application displays a comprehensive network for exploring the connection between angiogenesis and diseases at multilevels including protein–protein interaction, drug-target, disease-gene and signaling pathways among various cells and animal models recorded through text-mining. To enlarge the scope of the PubAngioGen application, our database also links to other common resources including STRING, DrugBank and OMIM databases, which will facilitate understanding the underlying molecular mechanisms of angiogenesis and drug development in clinical therapy.

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“…18,51 In addition, these pharmacoproteomic approaches were successfully employed to study the effects of antiplatelet therapy for finding the best management of cardiovascular diseases (CVDs) and other inflammatory diseases. 20,25,32,[40][41][42][48][49][50][51][52][53][54][55][56][57][58] It is very well known that platelets play a pivotal role in the pathophysiological mechanisms underlying many CVDs, especially acute coronary syndromes (ACSs), since platelets are the key players in thrombus formation after atheroma plaque rupture. 29,31,35 .…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, the recent advances in platelet proteomics applied to the study of CVDs focus primarily on sample preparation, subcellular fractionation, and bioinformatics requirements for proteome analysis of platelets derived from clinical samples. [30][31][32][33][34][35][36][37][38][39][40][41][52][53][54][55][56][57][58] To better understand the platelets' response to thrombin activation and its subsequent engagement of PAR receptors under clinical circumstances, especially when potent thrombin inhibitors can be used to treat the ACS syndrome, we developed and optimized a bottom-up, qualitative and quantitative label-free proteomic research study of human platelets isolated from healthy donors and ex-vivo activated with thrombin, using as reference the proteome of resting platelets. The label-free global proteomics analysis retrieved a total of 924 proteins, representing about 17% from the total proteins reported to date for platelets proteomes.…”

Section: Introductionmentioning

confidence: 99%

Development of a label‒free nanolc/ms/ms assay for monitoring the changes in the proteomic landscape of thrombin‒activated human platelets

Clement¹,

Gonzalez²,

Babińska³

et al. 2018

MOJPB

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One top research assay used to validate the efficacy of pharmacological agents used in antiplatelets aggregation therapy is mass spectrometry coupled with high throughput profiling of changes in the proteomic expression in the activated platelets exposed to inhibitors or agonists of platelets signaling. Herein we present the development of a new, bottom-up proteomics platform that enabled monitoring of changes in protein expression profiles of healthy human platelets, ex-vivo activated with thrombin, using as reference the proteome of resting platelets. The assay employed the platelets cryogenic lysis and protein solubilization under denaturant conditions, enabling the extraction of key membranebound proteins, in addition to the cytosolic and organelles-derived proteins secreted in microparticles, and found in the platelets releasates. Nano LC-ESI/MS/MS sequencing of tryptic/Glu-C/Lys-C peptides from the "in solution" one step digestion of the whole platelets proteomes (2x10 8 platelets/patient sample) was performed on a Q-Exactive quadrupole orbitrap mass spectrometer coupled with label free quantification (LFQ) analysis. The changes in proteomic landscapes were qualitatively and quantitatively analyzed using a combination of systems biology and bioinformatics approaches empowered by the ingenuity pathway analysis (IPA), and the screening of identified proteins and genes entities against curated databases containing platelets proteomes, including the "Adhesome", "Exocarta", "Reactome" and "Platelet Web". The label-free global proteomics analysis retrieved a total of 924 proteins (FDR <1.3% for proteins and <0.8% for peptides) out of which 330 were shared between resting and thrombin-activated platelets. About 50% of the total proteome of thrombin-activated platelets was represented by up-regulated and previously validated protein biomarkers, involved in the pathways mediating the protease and thrombin activated receptor (PARs), integrin signaling, the actin and rhoA linked to cytoskeleton signaling, and activated kinases pathways regulating the cellular motility, aggregation, procoagulation and degranulation. In conclusion, the systems biology approaches validated our newly developed LFQ proteomic assay as a reliable tool for monitoring the changes in protein expression profiles in thrombin-activated platelets, and further advocate for employment of these approaches in assessing the efficacy of antiplatelets drugs (inhibitors of platelets aggregation) during the prevention and treatment of cardiovascular and cerebrovascular diseases. Citation: Gonzalez J, Babinska A, Ewul ELV, et al. Development of a label-free nanolc/ms/ms assay for monitoring the changes in the proteomic landscape of thrombin-activated human platelets. MOJ Proteomics Bioinform. 2018;7(4):232-255. Platelets purification and ex-vivo activation with thrombin for proteomic analysisPRP were subjected to the whole platelets purification as described previously by other research groups. [30][31][32][33][34][35] Then, platelets were pelleted at 750xg ...

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Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

Cited by 23 publications

References 19 publications

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology

PubAngioGen: a database and knowledge for angiogenesis and related diseases

Development of a label‒free nanolc/ms/ms assay for monitoring the changes in the proteomic landscape of thrombin‒activated human platelets

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