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Published on: June 5, 2019
[Regulatory Effect of Protein Disulfide Isomerase on Platelet GPIbα Ectodomain Shedding]
Xia Wu1, Rong Yan1, Li-Li Zhao1
1Jiangsu Institute of Haematology, The First Affiliated Hospital of Soochow University; Key Laboratory of Thrombosis and Hemostasis, Ministry of Health; Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, Jiangsu Province, China.
Objective:
This study was aimed to investigate the regulatory effect of protein disulfide isomerase (PDI) on platelet GPIbα ectodomain shedding.
Methods:
The washed platelets were obtained from healthy volunteers. Platelets were incubated with PDI inhibitor bacitracin before stimulation with PMA (Phorbol-12-myristate-13-acetate), dibucaine and collagen. The N-terminal domain of GPIbα in supernatant was detected by Western blot, the GPIbα expression and the intraplatelet ROS levels were measured by flow cytometry.
Results:
neither GC content nor GPIbα expression was changed after the washed platelets from the healthy donors were incubated only with PDI inhibitor. The washed platelets were incubated with PDI inhibitor before stimulation with different stimulin, PMA, dibucaine or collagen, and then GPIbα was cleaved and ROS levels were elevated more than that in the controls.
Conclusion:
PDI participates in the induced GPIbα ectodomein shedding, and the effect of PDI in this process maybe depend on the change of ROS level inside platelets. These results might provide a new point of view for the platelet drug development.
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