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- Title
Role of Prednisolone in Platelet Activation by Inhibiting TxA 2 Generation through the Regulation of cPLA 2 Phosphorylation.
- Authors
Kim, Sanggu; Chaudhary, Preeti Kumari; Kim, Soochong
- Abstract
Simple Summary: Although glucocorticoids are frequently used for a variety of purposes, the effects and mechanisms of glucocorticoids on platelets are not fully understood. The present study investigates the effect of prednisolone and its mechanism of action on the regulation of platelet function. The results demonstrated that prednisolone affects platelet function by inhibiting thromboxane A2 (TxA2) generation through the regulation of cPLA2 phosphorylation, providing knowledge of glucocorticoids in coagulation and bleeding disorders. 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.
- Subjects
BLOOD platelet aggregation; BLOOD platelet activation; PREDNISOLONE; CUSHING'S syndrome; SHEAR waves; WESTERN immunoblotting
- Publication
Animals (2076-2615), 2023, Vol 13, Issue 8, p1299
- ISSN
2076-2615
- Publication type
Article
- DOI
10.3390/ani13081299