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

Humans Megakaryocytes Protein Kinase C / metabolism X-Rays Thrombocytopenia / etiology Thrombopoiesis Apoptosis Blood Platelets
Apoptosis Irradiation damage Megakaryocyte Platelet Protein kinase C

Journal

Blood cells, molecules & diseases
ISSN: 1096-0961
Titre abrégé: Blood Cells Mol Dis
Pays: United States
ID NLM: 9509932

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 15 05 2023
revised: 01 10 2023
accepted: 02 10 2023
medline: 6 12 2023
pubmed: 10 10 2023
entrez: 9 10 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.bcmd.2023.102798 PMID: 37813040
pubmed: 37813040
pii: S1079-9796(23)00075-X
doi: 10.1016/j.bcmd.2023.102798
pii:
doi:

Substances chimiques

2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide 0
Protein Kinase C EC 2.7.11.13

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102798

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no competing interests.

Auteurs

Fanbi Meng (F)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Shuang Chen (S)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Chunliang Liu (C)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Muhammad Shoaib Khan (MS)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Yan Yan (Y)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Jun Wan (J)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Yue Xia (Y)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Chenglin Sun (C)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Mengnan Yang (M)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Renping Hu (R)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China.

Kesheng Dai (K)

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Cyrus Tang Medical Institute, Soochow University, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215000, China. Electronic address: kdai@suda.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Mégacaryocytes › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Protéine kinase C › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Phénomènes physiques › Rayonnement › Rayonnement ionisant › Rayons X › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Anomalies des plaquettes › Thrombopénie › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Thrombopoïèse › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › The role of PKC in X-ray-induced megakaryocyte...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Cellules sanguines › Plaquettes › The role of PKC in X-ray-induced megakaryocyte...