1. The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia.
- Author
-
Meng, Fanbi, Chen, Shuang, Liu, Chunliang, Khan, Muhammad Shoaib, Yan, Yan, Wan, Jun, Xia, Yue, Sun, Chenglin, Yang, Mengnan, Hu, Renping, and Dai, Kesheng
- Subjects
- *
PROTEIN kinase C , *TOTAL body irradiation , *EXPOSURE therapy , *THROMBOCYTOPENIA , *APOPTOSIS - Abstract
Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF