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Article ; Online: Antiplatelet Effect of Daphnetin Is Regulated by cPLA 2 -Mediated Thromboxane A 2 Generation in Mice

Preeti Kumari Chaudhary / Sanggu Kim / Soochong Kim

International Journal of Molecular Sciences, Vol 24, Iss 5779, p

2023 Volume 5779

Abstract: Coumarin derivatives have been recognized for their antithrombotic, anti-inflammatory, and antioxidant properties, and daphnetin is one of the natural coumarin derivatives isolated from Daphne Koreana Nakai. Although the pharmacological value of ... ...

Abstract	Coumarin derivatives have been recognized for their antithrombotic, anti-inflammatory, and antioxidant properties, and daphnetin is one of the natural coumarin derivatives isolated from Daphne Koreana Nakai. Although the pharmacological value of daphnetin is well documented in diverse biological activities, its antithrombotic effect has not been studied to date. Here, we characterized the role and underlying mechanism of daphnetin in the regulation of platelet activation using murine platelets. In order to check the effect of daphnetin on platelet function, we first measured the effect of daphnetin on platelet aggregation and secretion. Collagen-induced platelet aggregation and dense granule secretion were partially inhibited by daphnetin. Interestingly, 2-MeSADP-induced secondary waves of aggregation and secretion were completely inhibited by daphnetin. It is known that 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by the positive feedback effect of thromboxane A 2 (TxA 2 ) generation, suggesting the important role of daphnetin on TxA 2 generation in platelets. Consistently, daphnetin did not affect the 2-MeSADP-induced platelet aggregation in aspirinated platelets where the contribution of TxA 2 generation was blocked. Additionally, platelet aggregation and secretion induced by a low concentration of thrombin, which is affected by the positive feedback effect of TxA 2 generation, were partially inhibited in the presence of daphnetin. Importantly, 2-MeSADP- and thrombin-induced TxA 2 generation was significantly inhibited in the presence of daphnetin, confirming the role of daphnetin on TxA 2 generation. Finally, daphnetin significantly inhibited 2-MeSADP-induced cytosolic phospholipase A 2 (cPLA 2 ) and ERK phosphorylation in non-aspirinated platelets. Only cPLA 2 phosphorylation, not ERK phosphorylation, was significantly inhibited by daphnetin in aspirinated platelets. In conclusion, daphnetin plays a critical role in platelet function by inhibiting TxA 2 generation ...
Keywords	daphnetin ; thromboxane A 2 ; cPLA 2 ; ERK ; 2-MeSADP ; platelet ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	290
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Shedding Light on the Cell Biology of Platelet-Derived Extracellular Vesicles and Their Biomedical Applications

Preeti Kumari Chaudhary / Sanggu Kim / Soochong Kim

Life, Vol 13, Iss 1403, p

2023 Volume 1403

Abstract: EVs are membranous subcellular structures originating from various cells, including platelets which consist of biomolecules that can modify the target cell’s pathophysiological functions including inflammation, cell communication, coagulation, and ... ...

Abstract	EVs are membranous subcellular structures originating from various cells, including platelets which consist of biomolecules that can modify the target cell’s pathophysiological functions including inflammation, cell communication, coagulation, and metastasis. EVs, which are known to allow the transmission of a wide range of molecules between cells, are gaining popularity in the fields of subcellular treatment, regenerative medicine, and drug delivery. PEVs are the most abundant EVs in circulation, being produced by platelet activation, and are considered to have a significant role in coagulation. PEV cargo is extremely diverse, containing lipids, proteins, nucleic acids, and organelles depending on the condition that induced their release and can regulate a wide range of biological activities. PEVs, unlike platelets, can overcome tissue barriers, allowing platelet-derived contents to be transferred to target cells and organs that platelets cannot reach. Their isolation, characterization, and therapeutic efficacy, on the other hand, are poorly understood. This review summarizes the technical elements of PEV isolation and characterization methods as well as the pathophysiological role of PEVs, including therapeutic potential and translational possibility in diverse disciplines.
Keywords	platelets ; PEVs ; hemostasis ; inflammation ; angiogenesis ; wound healing ; Science ; Q
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Perspectives of Platelet Proteomics in Health and Disease.

Chaudhary, Preeti Kumari / Upadhayaya, Sachin / Kim, Sanggu / Kim, Soochong

Biomedicines

2024 Volume 12, Issue 3

Abstract: Cardiovascular thromboembolic diseases and cancer continue to be a leading cause of death and disability worldwide. Therefore, it is crucial to advance their diagnoses and treatment in the context of individualized medicine. However, the disease ... ...

Abstract	Cardiovascular thromboembolic diseases and cancer continue to be a leading cause of death and disability worldwide. Therefore, it is crucial to advance their diagnoses and treatment in the context of individualized medicine. However, the disease specificity of the currently available markers is limited. Based on analyses of a subset of peptides and matching proteins in disease vs. healthy platelets, scientists have recently shown that focused platelet proteomics enables the quantification of disease-specific biomarkers in humans. In this review, we explored the potential of accurate platelet proteomic research, which is required to identify novel diagnostic and pharmaceutical targets by comprehending the proteome variety of healthy individuals and patients for personalized and precision medicine.
Language	English
Publishing date	2024-03-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12030585
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The GRKs Reactome

Preeti Kumari Chaudhary / Soochong Kim

International Journal of Molecular Sciences, Vol 22, Iss 3375, p

Role in Cell Biology and Pathology

2021 Volume 3375

Abstract: G protein-coupled receptor kinases (GRKs) are protein kinases that function in concert with arrestins in the regulation of a diverse class of G protein-coupled receptors (GPCRs) signaling. Although GRKs and arrestins are key participants in the ... ...

Abstract	G protein-coupled receptor kinases (GRKs) are protein kinases that function in concert with arrestins in the regulation of a diverse class of G protein-coupled receptors (GPCRs) signaling. Although GRKs and arrestins are key participants in the regulation of GPCR cascades, the complex regulatory mechanisms of GRK expression, its alternation, and their function are not thoroughly understood. Several studies together with the work from our lab in recent years have revealed the critical role of these kinases in various physiological and pathophysiological processes, including cardiovascular biology, inflammation and immunity, neurodegeneration, thrombosis, and hemostasis. A comprehensive understanding of the mechanisms underlying functional interactions with multiple receptor proteins and how these interactions take part in the development of various pathobiological processes may give rise to novel diagnostic and therapeutic strategies. In this review, we summarize the current research linking the role of GRKs to various aspects of cell biology, pathology, and therapeutics, with a particular focus on thrombosis and hemostasis.
Keywords	GRKs ; GPCR ; arrestins ; G protein ; cell biology ; pathology ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An Insight into GPCR and G-Proteins as Cancer Drivers

Preeti Kumari Chaudhary / Soochong Kim

Cells, Vol 10, Iss 3288, p

2021 Volume 3288

Abstract: G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis. Various molecules such as hormones, lipids, peptides, ... ...

Abstract	G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis. Various molecules such as hormones, lipids, peptides, and neurotransmitters activate GPCRs that enable the coupling of these receptors to highly specialized transducer proteins, called G-proteins, and initiate multiple signaling pathways. Integration of these intricate networks of signaling cascades leads to numerous biochemical responses involved in diverse pathophysiological activities, including cancer development. While several studies indicate the role of GPCRs in controlling various aspects of cancer progression such as tumor growth, invasion, migration, survival, and metastasis through its aberrant overexpression, mutations, or increased release of agonists, the explicit mechanisms of the involvement of GPCRs in cancer progression is still puzzling. This review provides an insight into the various responses mediated by GPCRs in the development of cancers, the molecular mechanisms involved and the novel pharmacological approaches currently preferred for the treatment of cancer. Thus, these findings extend the knowledge of GPCRs in cancer cells and help in the identification of therapeutics for cancer patients.
Keywords	GPCR ; G-protein ; GPCR signaling ; cancer ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Role of Prednisolone in Platelet Activation by Inhibiting TxA

Kim, Sanggu / Chaudhary, Preeti Kumari / Kim, Soochong

Animals : an open access journal from MDPI

2023 Volume 13, Issue 8

Abstract: Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing's syndrome along with several thrombotic and ... ...

Abstract	Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing's syndrome along with several thrombotic and cardiovascular diseases. Although it is well-known that glucocorticoids exert a significant effect on coagulation, the effect of cortisol on platelet function is much less clear. Thus, we aimed to study the effects of prednisolone, one of the commonly used glucocorticoids, on the regulation of platelet function using murine platelets. We first evaluated the concentration-dependent effect of prednisolone on 2-MeSADP-induced platelet function and found that the 2-MeSADP-induced secondary wave of aggregation and dense granule secretion were completely inhibited from 500 nM prednisolone. Since 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by TxA
Language	English
Publishing date	2023-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13081299
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Article ; Online: Antiplatelet Effect of Daphnetin Is Regulated by cPLA

Chaudhary, Preeti Kumari / Kim, Sanggu / Kim, Soochong

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Coumarin derivatives have been recognized for their antithrombotic, anti-inflammatory, and antioxidant properties, and daphnetin is one of the natural coumarin derivatives isolated ... ...

Abstract	Coumarin derivatives have been recognized for their antithrombotic, anti-inflammatory, and antioxidant properties, and daphnetin is one of the natural coumarin derivatives isolated from
MeSH term(s)	Animals ; Mice ; Blood Platelets ; Fibrinolytic Agents/pharmacology ; Platelet Aggregation ; Thrombin/pharmacology ; Thromboxane A2 ; Thromboxanes ; Umbelliferones/pharmacology ; Phospholipases A2, Cytosolic/metabolism
Chemical Substances	daphnetin (XC84571RD2) ; Fibrinolytic Agents ; methylthio-ADP (34983-48-7) ; Thrombin (EC 3.4.21.5) ; Thromboxane A2 (57576-52-0) ; Thromboxanes ; Umbelliferones ; Phospholipases A2, Cytosolic (EC 3.1.1.4)
Language	English
Publishing date	2023-03-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065779
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Shedding Light on the Cell Biology of Platelet-Derived Extracellular Vesicles and Their Biomedical Applications.

Chaudhary, Preeti Kumari / Kim, Sanggu / Kim, Soochong

Life (Basel, Switzerland)

2023 Volume 13, Issue 6

Abstract: EVs are membranous subcellular structures originating from various cells, including platelets which consist of biomolecules that can modify the target cell's pathophysiological functions including inflammation, cell communication, coagulation, and ... ...

Abstract	EVs are membranous subcellular structures originating from various cells, including platelets which consist of biomolecules that can modify the target cell's pathophysiological functions including inflammation, cell communication, coagulation, and metastasis. EVs, which are known to allow the transmission of a wide range of molecules between cells, are gaining popularity in the fields of subcellular treatment, regenerative medicine, and drug delivery. PEVs are the most abundant EVs in circulation, being produced by platelet activation, and are considered to have a significant role in coagulation. PEV cargo is extremely diverse, containing lipids, proteins, nucleic acids, and organelles depending on the condition that induced their release and can regulate a wide range of biological activities. PEVs, unlike platelets, can overcome tissue barriers, allowing platelet-derived contents to be transferred to target cells and organs that platelets cannot reach. Their isolation, characterization, and therapeutic efficacy, on the other hand, are poorly understood. This review summarizes the technical elements of PEV isolation and characterization methods as well as the pathophysiological role of PEVs, including therapeutic potential and translational possibility in diverse disciplines.
Language	English
Publishing date	2023-06-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13061403
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Role of Prednisolone in Platelet Activation by Inhibiting TxA2 Generation through the Regulation of cPLA2 Phosphorylation

Kim, Sanggu / Chaudhary, Preeti Kumari / Kim, Soochong

Animals. 2023 Apr. 11, v. 13, no. 8

2023

Abstract: Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing’s syndrome along with several thrombotic and ... ...

Abstract	Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing’s syndrome along with several thrombotic and cardiovascular diseases. Although it is well-known that glucocorticoids exert a significant effect on coagulation, the effect of cortisol on platelet function is much less clear. Thus, we aimed to study the effects of prednisolone, one of the commonly used glucocorticoids, on the regulation of platelet function using murine platelets. We first evaluated the concentration-dependent effect of prednisolone on 2-MeSADP-induced platelet function and found that the 2-MeSADP-induced secondary wave of aggregation and dense granule secretion were completely inhibited from 500 nM prednisolone. Since 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by TxA₂ generation, this result suggested a role of prednisolone in platelet TxA₂ generation. Consistently, prednisolone did not affect the 2-MeSADP-induced aggregation in aspirinated platelets, where the secondary wave of aggregation and secretion were blocked by eliminating the contribution of TxA₂ generation by aspirin. In addition, thrombin-induced platelet aggregation and secretion were inhibited in the presence of prednisolone by inhibiting the positive-feedback effect of TxA₂ generation on platelet function. Furthermore, prednisolone completely inhibited 2-MeSADP-induced TxA₂ generation, confirming the role of prednisolone in TxA₂ generation. Finally, Western blot analysis revealed that prednisolone significantly inhibited 2-MeSADP-induced cytosolic phospholipase A₂ (cPLA₂) and ERK phosphorylation in non-aspirinated platelets, while only cPLA₂ phosphorylation, but not ERK phosphorylation, was significantly inhibited by prednisolone in aspirinated platelets. In conclusion, prednisolone affects platelet function by the inhibition of TxA₂ generation through the regulation of cPLA₂ phosphorylation, thereby shedding light on its clinical characterization and treatment efficacy in dogs with hypercortisolism in the future.
Keywords	Cushing syndrome ; Western blotting ; aspirin ; coagulation ; cortisol ; humans ; inflammation ; mice ; phospholipases ; phosphorylation ; platelet aggregation ; prednisolone ; secretion
Language	English
Dates of publication	2023-0411
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13081299
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An Insight into Recent Advances on Platelet Function in Health and Disease

Preeti Kumari Chaudhary / Sanggu Kim / Soochong Kim

International Journal of Molecular Sciences, Vol 23, Iss 6022, p

2022 Volume 6022

Abstract: Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis and thrombosis mediators. Platelets have a large number of receptors and secretory molecules that are required for platelet functionality. Upon activation, ...

Abstract	Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis and thrombosis mediators. Platelets have a large number of receptors and secretory molecules that are required for platelet functionality. Upon activation, platelets release multiple substances that have the ability to influence both physiological and pathophysiological processes including inflammation, tissue regeneration and repair, cancer progression, and spreading. The involvement of platelets in the progression and seriousness of a variety of disorders other than thrombosis is still being discovered, especially in the areas of inflammation and the immunological response. This review represents an integrated summary of recent advances on the function of platelets in pathophysiology that connects hemostasis, inflammation, and immunological response in health and disease and suggests that antiplatelet treatment might be used for more than only thrombosis.
Keywords	platelet ; CVDs ; inflammation ; diabetes mellitus ; cancer ; wound healing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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