Increased autophagy leads to decreased apoptosis during β-thalassaemic mouse and patient erythropoiesis
2
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85141220317
Pubmed ID
36329049
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Chaichompoo P., Nithipongvanitch R., Kheansaard W., Tubsuwan A., Srinoun K., Vadolas J., Fucharoen S., Smith D.R., Winichagoon P., Svasti S. Increased autophagy leads to decreased apoptosis during β-thalassaemic mouse and patient erythropoiesis. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-21249-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86385
Title
Increased autophagy leads to decreased apoptosis during β-thalassaemic mouse and patient erythropoiesis
Other Contributor(s)
Abstract
β-Thalassaemia results from defects in β-globin chain production, leading to ineffective erythropoiesis and subsequently to severe anaemia and other complications. Apoptosis and autophagy are the main pathways that regulate the balance between cell survival and cell death in response to diverse cellular stresses. Herein, the death of erythroid lineage cells in the bone marrow from both βIVS2-654-thalassaemic mice and β-thalassaemia/HbE patients was investigated. Phosphatidylserine (PS)-bearing basophilic erythroblasts and polychromatophilic erythroblasts were significantly increased in β-thalassaemia as compared to controls. However, the activation of caspase 8, caspase 9 and caspase 3 was minimal and not different from control in both murine and human thalassaemic erythroblasts. Interestingly, bone marrow erythroblasts from both β-thalassaemic mice and β-thalassaemia/HbE patients had significantly increased autophagy as shown by increased autophagosomes and increased co-localization between LC3 and LAMP-1. Inhibition of autophagy by chloroquine caused significantly increased erythroblast apoptosis. We have demonstrated increased autophagy which led to minimal apoptosis in β-thalassaemic erythroblasts. However, increased PS exposure occurring through other mechanisms in thalassaemic erythroblasts might cause rapid phagocytic removal by macrophages and consequently ineffective erythropoiesis in β-thalassaemia.