The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia

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 megak...

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Published in:Blood cells, molecules, & diseases molecules, & diseases, 2024-01, Vol.104, p.102798-102798, Article 102798
Main Authors: Meng, Fanbi, Chen, Shuang, Liu, Chunliang, Khan, Muhammad Shoaib, Yan, Yan, Wan, Jun, Xia, Yue, Sun, Chenglin, Yang, Mengnan, Hu, Renping, Dai, Kesheng
Format: Article
Language:English
Subjects:
Apoptosis
Blood Platelets
Humans
Irradiation damage
Megakaryocyte
Megakaryocytes
Platelet
Protein kinase C
Protein Kinase C - metabolism
Protein Kinase C - therapeutic use
Thrombocytopenia - etiology
Thrombopoiesis
X-Rays
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Summary: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.
ISSN:1079-9796
1096-0961
DOI:10.1016/j.bcmd.2023.102798