The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia.
Blood Cells Mol Dis
; 104: 102798, 2024 01.
Article
in En
| MEDLINE
| ID: mdl-37813040
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombocytopenia
/
Megakaryocytes
Limits:
Humans
Language:
En
Journal:
Blood Cells Mol Dis
/
Blood cells mol. dis
/
Blood cells, molecules & diseases
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos