Cysteine and methionine oxidation in thrombotic disorders

Article Hematology

Sulfenylation links oxidative stress to protein disulfide isomerase oxidase activity and thrombus formation

Moua Yang et al.

Summary: Oxidative stress leads to protein damage and inactivation. PDI is disrupted during oxidative stress, resulting in thrombus formation. Inhibiting PDI disruption can reduce thrombus formation.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2023)

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Article Immunology

Beta-2-glycoprotein I exerts antithrombotic function through its domain V in mice

Freda H. Passam et al.

Summary: This study found that ss2GPI deficient mice have enhanced thrombus formation compared to wild type mice, and the antithrombotic function of ss2GPI is mainly dependent on its fifth domain.

JOURNAL OF AUTOIMMUNITY (2022)

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Article Cell Biology

Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology

Helmut Sies et al.

Summary: This article discusses the key issues associated with identifying the physiological roles of oxidants, with a focus on H2O2 and O-2(.-). The article emphasizes the need for more precise measurement of oxidants and specific identification of their signaling targets. It also highlights the importance of inter-organellar communication and the contribution of environmental exposures. Development of tools for real-time detection and quantification of individual oxidants is crucial for achieving these goals.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

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Review Cell Biology

Endothelial cells and coagulation

Katharina Neubauer et al.

Summary: Endothelial cells play a crucial role in maintaining blood fluidity and controlled vascular hemostasis, balancing procoagulant and anticoagulant mechanisms. They prevent platelet activation and promote fibrinolytic and antithrombotic properties, while also supporting clot formation at sites of vascular damage.

CELL AND TISSUE RESEARCH (2022)

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Article Immunology

Cardiovascular disease risk in antiphospholipid syndrome: Thrombo-inflammation and atherothrombosis

Maria G. Tektonidou

Summary: Antiphospholipid syndrome (APS), an autoimmune disorder, primarily affects young adults and is characterized by the presence of antiphospholipid antibodies along with vascular manifestations. The pathogenesis of cardiovascular disease (CVD) in APS involves factors such as platelet activation, thrombosis, and the role of oxidized low-density lipoprotein. In addition, traditional risk factors including smoking, hypertension, hyperlipemia, and obesity are associated with subclinical atherosclerosis and cardiovascular events in APS.

JOURNAL OF AUTOIMMUNITY (2022)

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Article Biochemistry & Molecular Biology

The extracellular Ero1α/PDI electron transport system regulates platelet function by increasing glutathione reduction potential

Lu Wang et al.

Summary: Protein disulfide isomerase (PDI) plays a critical role in platelet aggregation, thrombosis, and hemostasis, and inhibiting PDI may be a novel antithrombotic strategy. The interaction between endoplasmic reticulum oxidoreductin-1 alpha (Ero1 alpha) and PDI in mediating platelet aggregation through an extracellular electron transport pathway is investigated. The study reveals that oxidized PDI promotes platelet aggregation, and Ero1 alpha regulates platelet aggregation in a glutathione-dependent manner.

REDOX BIOLOGY (2022)

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Article Chemistry, Multidisciplinary

An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4

Angel Gonzalez-Valero et al.

Summary: Activity-based protein profiling (ABPP) is a versatile strategy for identifying and characterizing functional protein sites and compounds for therapeutic development. This study introduces a methionine-specific ABPP platform and successfully identifies new ligandable methionine sites. The work also presents a unique therapeutic intervention method, laying the foundation for discovering and targeting previously undruggable methionine sites.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

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Article Cell Biology

Oxidation and reduction of actin: Origin, impact in vitro and functional consequences in vivo

Clementine Rouyere et al.

Summary: Actin, a highly abundant protein, plays a crucial role in cellular functions. Oxidation modifications affect actin polymerization and the cellular cytoskeleton, while the balance between oxidation and reduction of key actin amino acid residues contributes to the control of actin filament assembly and disassembly.

EUROPEAN JOURNAL OF CELL BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Reduction of protein disulfide isomerase results in open conformations and stimulates dynamic exchange between structural ensembles

Mathivanan Chinnaraj et al.

Summary: This study used multiparameter confocal single-molecule FRET to track the movements of the two catalytic domains of human protein disulfide isomerase (PDI) with high temporal resolution. The results showed that PDI visits three structurally distinct conformational ensembles, with the redox environment dictating the time spent in each ensemble and the rate of exchange between them. Additionally, the study found that specific interactions and cysteine residues play unexpected roles in the relocation of the catalytic domains.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

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Review Cell Biology

The Role of NO/sGC/cGMP/PKG Signaling Pathway in Regulation of Platelet Function

Stepan Gambaryan

Summary: Circulating blood platelets are regulated by stimulatory and inhibitory factors, and maintaining a balance between these processes is crucial for normal platelet and vascular function. The NO/cGMP/PKG signaling pathway plays a significant role in platelet inhibition, but its regulation is still not well understood.

CELLS (2022)

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Review Biochemistry & Molecular Biology

Platelets and Their Role in Hemostasis and Thrombosis-From Physiology to Pathophysiology and Therapeutic Implications

Alina Scridon

Summary: This article comprehensively explores the complex role of platelets in hemostasis and thrombosis, discussing their importance in clinical medicine, and studying hemostatic platelet-related disorders and antithrombotic therapies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Hematology

Sulfenylome analysis of pathogen-inactivated platelets reveals the presence of cysteine oxidation in integrin signaling pathway and cytoskeleton regulation

Giona Sonego et al.

Summary: This study developed a workflow to identify and quantify sulfenic acid-containing proteins in platelet concentrates, discovering 174 sulfenylated proteins mainly involved in integrin signaling pathway and cytoskeletal regulation by Rho GTPase. The impact of pathogen inactivated platelet concentrates was minimal compared to untreated ones, with three significantly affected proteins.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2021)

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Article Biochemistry & Molecular Biology

Oxidation shuts down an auto-inhibitory mechanism of von Willebrand factor

Rachel Tsai et al.

Summary: Methionine oxidation removes the auto-inhibitory mechanism of VWF, leading to the exposure of the GpIb alpha-binding site in the A1 domain, without directly activating the A1 domain.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2021)

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Article Multidisciplinary Sciences

Specific domain V reduction of beta-2-glycoprotein I induces protein flexibility and alters pathogenic antibody binding

Ina Buchholz et al.

Summary: This study reports enzymatic-driven reduction of beta 2GPI by thioredoxin-1, resulting in a higher proportion of open conformation and increased flexibility in the protein. The binding of pathogenic APS autoantibodies to reduced beta 2GPI was significantly enhanced, indicating a potential impact on antibody binding in APS patients.

SCIENTIFIC REPORTS (2021)

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Review Biochemistry & Molecular Biology

Structural insights into redox-active cysteine residues of the Src family kinases

David E. Heppner

Summary: The activity of SFKs kinases is regulated by protein phosphorylation, and the oxidation state of their redox-active cysteine residues is influenced by the local structural environment. Conserved and non-conserved cysteine residues exhibit differences in oxidation activity and structural environments.

REDOX BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Thiol Isomerases Orchestrate Thrombosis and Hemostasis

Renato Simoes Gaspar et al.

Summary: Protein disulfide isomerase (PDI) and sibling proteins play essential roles in thrombus formation by influencing protein folding and function at the cell surface. Thiol isomerase targets have been identified, demonstrating their significance in regulating thrombosis.

ANTIOXIDANTS & REDOX SIGNALING (2021)

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Review Biochemistry & Molecular Biology

Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process

Cristina Nocella et al.

Summary: Atherothrombosis is a common complication in patients with antiphospholipid syndrome (APS) and is associated with increased oxidative stress. Oxidative modifications contribute to the formation of antiphospholipid antibodies, leading to oxidative imbalance, which may contribute to the progression of atherosclerosis and ischemic thrombotic complications in APS patients.

ANTIOXIDANTS (2021)

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Article Biochemistry & Molecular Biology

Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress

Aishwarya R. Vaidya et al.

Summary: Diabetes mellitus is the fifth most common cause of death globally, with type 2 diabetes being the most prevalent form. Diabetes patients have a higher risk of developing cardiovascular disease, largely due to platelet hyperactivity.

ANTIOXIDANTS (2021)

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Article Biochemistry & Molecular Biology

Oxidative Cysteine Modification of Thiol Isomerases in Thrombotic Disease: A Hypothesis

Moua Yang et al.

Summary: Oxidative stress is a characteristic of many systemic diseases associated with thrombosis, and thiol isomerases play a key role in protein folding. Recent studies show that the oxidoreductase activity of thiol isomerases in thrombus formation is controlled by the redox environment and may potentially control thrombotic potential by modifying substrate networks.

ANTIOXIDANTS & REDOX SIGNALING (2021)

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Article Biochemistry & Molecular Biology

An allosteric redox switch in domain V of β2-glycoprotein I controls membrane binding and anti-domain I autoantibody recognition

Suresh Kumar et al.

Summary: The study reveals the distinct roles of the two disulfide bonds, C32-C60 and C288-C326, in regulating the structure and function of β(2)GPI. While the C32-C60 bond plays a structural role, the C288-C326 bond functions as an allosteric switch controlling the protein's physiological functions in a redox-dependent manner.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Multidisciplinary Sciences

Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods

Wai-Hoe Lau et al.

Summary: The study investigates the impact of HOCl oxidation on fibrinogen structure and function, revealing that oxidized fibrinogen is more compact and moves faster in the prefibrillar state. Additionally, oxidation leads to thinner fibers, reduced release of water into the bulk, and increased water fraction in the hydration shell.

SCIENTIFIC REPORTS (2021)

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Review Hematology

Platelet Src family kinases: A tale of reversible phosphorylation

Yotis A. Senis et al.

Summary: SFKs, originally discovered as proto-oncogenes, play vital roles in platelet research by initiating and amplifying signals from major receptors, providing insights into self-regulation through phosphorylation of their C-terminal tyrosine residues, and offering potential therapeutic targets for regulating platelet functions.

RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS (2021)

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Review Hematology

The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS

Thomas McDonnell et al.

BLOOD REVIEWS (2020)

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Review Chemistry, Multidisciplinary

Activity-Based Sensing for Site-Specific Proteomic Analysis of Cysteine Oxidation

Yunlong Shi et al.

ACCOUNTS OF CHEMICAL RESEARCH (2020)

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Article Hematology

Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia

Moua Yang et al.

BLOOD ADVANCES (2020)

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Review Biochemistry & Molecular Biology

Effect of Prostanoids on Human Platelet Function: An Overview

Steffen Braune et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Biochemistry & Molecular Biology

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

Xu Cao et al.

ANTIOXIDANTS & REDOX SIGNALING (2019)

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Review Biochemistry & Molecular Biology

CD36 signaling in vascular redox stress

Moua Yang et al.

FREE RADICAL BIOLOGY AND MEDICINE (2019)

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Review Medical Laboratory Technology

Post-translational modifications of proteins in antiphospholipid antibody syndrome

Brigitta Buttari et al.

CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES (2019)

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Article Hematology

An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1

Ze Zheng et al.

BLOOD (2019)

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Review Biochemistry & Molecular Biology

Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation

Joyce Chiu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Multidisciplinary Sciences

Cysteine Disulfides (Cys-ss-X) as Sensitive Plasma Biomarkers of Oxidative Stress

Xiaoyun Fu et al.

SCIENTIFIC REPORTS (2019)

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Review Hematology

Fibrinogen and fibrin: An illustrated review

Marlien Pieters et al.

RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS (2019)

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Article Hematology

Protein disulfide isomerase regulation by nitric oxide maintains vascular quiescence and controls thrombus formation

R. H. Bekendam et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2018)

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Article Multidisciplinary Sciences

Direct cysteine sulfenylation drives activation of the Src kinase

David E. Heppner et al.

NATURE COMMUNICATIONS (2018)

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Article Hematology

Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo

Moua Yang et al.

BLOOD ADVANCES (2018)

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Article Hematology

Novel antiplatelet role for a protein disulfide isomerase-targeted peptide: evidence of covalent binding to the C-terminal CGHC redox motif

H. R. Sousa et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2017)

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Article Biochemistry & Molecular Biology

Nitrosothiol formation and S-nitrosation signaling through nitric oxide synthases

Sarah L. Wynia-Smith et al.

NITRIC OXIDE-BIOLOGY AND CHEMISTRY (2017)

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Article Multidisciplinary Sciences

Redox-based reagents for chemoselective methionine bioconjugation

Shixian Lin et al.

SCIENCE (2017)

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Article Hematology

Platelet CD36 promotes thrombosis by activating redox sensor ERK5 in hyperlipidemic conditions

Moua Yang et al.

BLOOD (2017)

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Review Biochemistry & Molecular Biology

Platelet Shape Changes and Cytoskeleton Dynamics as Novel Therapeutic Targets for Anti-Thrombotic Drugs

Eun-Kyung Shin et al.

BIOMOLECULES & THERAPEUTICS (2017)

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Article Chemistry, Medicinal

Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification

Ryan S. Wible et al.

CHEMICAL RESEARCH IN TOXICOLOGY (2017)

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Article Biochemistry & Molecular Biology

Biological chemistry of hydrogen sulfide and persulfides

Ernesto Cuevasanta et al.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2017)

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Article Cardiac & Cardiovascular Systems

Global Burden of Thrombosis Epidemiologic Aspects

Aaron M. Wendelboe et al.

CIRCULATION RESEARCH (2016)

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Article Hematology

Deficiency of Superoxide Dismutase Impairs Protein C Activation and Enhances Susceptibility to Experimental Thrombosis

Sanjana Dayal et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2015)

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Review Hematology

Regulation of thrombosis and vascular function by protein methionine oxidation

Sean X. Gu et al.

BLOOD (2015)

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Article Hematology

Oxidized LDL activates blood platelets through CD36/NOX2-mediated inhibition of the cGMP/protein kinase G signaling cascade

Simbarashe Magwenzi et al.

BLOOD (2015)

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Article Biochemistry & Molecular Biology

Hypochlorous Acid Generated by Neutrophils Inactivates ADAMTS13 AN OXIDATIVE MECHANISM FOR REGULATING ADAMTS13 PROTEOLYTIC ACTIVITY DURING INFLAMMATION

Yi Wang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2015)

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Article Chemistry, Multidisciplinary

Detection of Protein S-Sulfhydration by a Tag-Switch Technique

Dehui Zhang et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2014)

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Article Cell Biology

Effect of the hydrogen sulfide donor GYY4137 on platelet activation and microvascular thrombus formation in mice

Eberhard Grambow et al.

PLATELETS (2014)

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Review Chemistry, Multidisciplinary

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Candice E. Paulsen et al.

CHEMICAL REVIEWS (2013)

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Review Biochemistry & Molecular Biology

Functional impact of oxidative posttranslational modifications on fibrinogen and fibrin clots

Marissa Martinez et al.

FREE RADICAL BIOLOGY AND MEDICINE (2013)

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Article Biophysics

Fibrin Clot Structure and Mechanics Associated with Specific Oxidation of Methionine Residues in Fibrinogen

Katie M. Weigandt et al.

BIOPHYSICAL JOURNAL (2012)

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Review Biochemistry & Molecular Biology

Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling

Brian C. Smith et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2012)

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Review Biophysics

Actin Structure and Function

Roberto Dominguez et al.

ANNUAL REVIEW OF BIOPHYSICS, VOL 40 (2011)

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Article Hematology

Shear stress-induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region

Xiaoyun Fu et al.

BLOOD (2011)

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Article Biochemistry & Molecular Biology

Cysteine sulfenic Acid as an Intermediate in Disulfide Bond Formation and Nonenzymatic Protein Folding

Douglas S. Rehder et al.

BIOCHEMISTRY (2010)

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Letter Hematology

Beta 2 glycoprotein I is a substrate of thiol oxidoreductases

Freda H. Passam et al.

BLOOD (2010)

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Article Hematology

Naturally occurring free thiols within β2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress-induced cell injury

Yiannis Ioannou et al.

BLOOD (2010)

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Article Hematology

von Willebrand factor assembly and secretion

J. E. Sadler

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2009)

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Article Biochemistry & Molecular Biology

Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype

Eugene A. Podrez et al.

NATURE MEDICINE (2007)

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Article Pharmacology & Pharmacy

Protein S-glutathionylation and platelet anti-aggregating activity of disulfiram

Ranieri Rossi et al.

BIOCHEMICAL PHARMACOLOGY (2006)

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Article Biochemistry & Molecular Biology

S-glutathionylation in human platelets by a thiol-disulfide exchange-independent mechanism

I Dalle-Donne et al.

FREE RADICAL BIOLOGY AND MEDICINE (2005)

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Cysteine and methionine oxidation in thrombotic disorders

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