University Presentation Showcase: Undergraduate Division

The Impact of Ergothioneine on Platelet Dense Granule Secretion and Aggregation Dynamics

Presenter Hometown

Breathitt County

Major

Biomedical Sciences

Department

Biological Sciences

Degree

Undergraduate

Mentor

Smita Joshi

Mentor Department

Biological Sciences

Abstract

Cardiovascular diseases such as heart attacks and strokes represent a significant global health burden and are frequently driven by thrombotic events. This burden is especially pronounced in regions such as Kentucky, ranking 48th in the nation for cardiovascular health.  Thrombosis is the pathological formation of blood clots that obstruct blood vessels. Central to this process are platelets; small cell fragments crucial for normal hemostasis. Because platelet aggregation is tightly regulated, both insufficient and excessive activation can lead to bleeding or thrombosis. Current antithrombotic therapies are effective in preventing thrombosis but are often associated with an increased risk of bleeding, highlighting the need for safer alternatives. Ergothioneine is mainly derived from mushrooms and is a well-known antioxidant. It has been shown to inhibit platelet activity; however, the underlying mechanism is unclear. In this project, we aim to uncover the molecular mechanism of its action on platelets.

To study this, platelets will be isolated from plasma using serial centrifugation. The isolated platelets will then be treated with varying concentrations of ergothioneine, and platelet function will be monitored using lumi-aggregometry. This technique will measure both platelet aggregation and ATP release from dense granules following stimulation with thrombin (a GPCR-mediated agonist) and collagen (a GPVI-mediated agonist). Data will be analyzed to identify trends in platelet responsiveness and to determine the effects of ergothioneine.

The findings from this study may provide insight into the potential use of ergothioneine and similar compounds as therapeutic agents for maintaining platelet homeostasis in disorders associated with dysregulated clotting.

This project is supported by the National Institute of General Medical Sciences of the National Institutes of Health Award # P20GM103436.

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Poster

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The Impact of Ergothioneine on Platelet Dense Granule Secretion and Aggregation Dynamics

Cardiovascular diseases such as heart attacks and strokes represent a significant global health burden and are frequently driven by thrombotic events. This burden is especially pronounced in regions such as Kentucky, ranking 48th in the nation for cardiovascular health.  Thrombosis is the pathological formation of blood clots that obstruct blood vessels. Central to this process are platelets; small cell fragments crucial for normal hemostasis. Because platelet aggregation is tightly regulated, both insufficient and excessive activation can lead to bleeding or thrombosis. Current antithrombotic therapies are effective in preventing thrombosis but are often associated with an increased risk of bleeding, highlighting the need for safer alternatives. Ergothioneine is mainly derived from mushrooms and is a well-known antioxidant. It has been shown to inhibit platelet activity; however, the underlying mechanism is unclear. In this project, we aim to uncover the molecular mechanism of its action on platelets.

To study this, platelets will be isolated from plasma using serial centrifugation. The isolated platelets will then be treated with varying concentrations of ergothioneine, and platelet function will be monitored using lumi-aggregometry. This technique will measure both platelet aggregation and ATP release from dense granules following stimulation with thrombin (a GPCR-mediated agonist) and collagen (a GPVI-mediated agonist). Data will be analyzed to identify trends in platelet responsiveness and to determine the effects of ergothioneine.

The findings from this study may provide insight into the potential use of ergothioneine and similar compounds as therapeutic agents for maintaining platelet homeostasis in disorders associated with dysregulated clotting.

This project is supported by the National Institute of General Medical Sciences of the National Institutes of Health Award # P20GM103436.