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

  • Impact factors: 2.3
  • Publication: BLOOD CELLS MOLECULES AND DISEASES
  • Author:Fanbi Meng, Shuang Chen, Chunliang Liu, Muhammad Shoaib Khan, Yan Yan, Jun Wan, Yue Xia, Chenglin Sun, Mengnan Yang, Renping Hu, Kesheng Dai
  • DOI citation-doi:10.1016/j.bcmd.2023.102798
  • Date:2023-10-04

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.

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