| First Author | Chaichompoo P | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 18628 |
| PubMed ID | 36329049 | Mgi Jnum | J:330721 |
| Mgi Id | MGI:7384024 | Doi | 10.1038/s41598-022-21249-6 |
| Citation | Chaichompoo P, et al. (2022) Increased autophagy leads to decreased apoptosis during beta-thalassaemic mouse and patient erythropoiesis. Sci Rep 12(1):18628 |
| abstractText | beta-Thalassaemia results from defects in beta-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 beta(IVS2-654)-thalassaemic mice and beta-thalassaemia/HbE patients was investigated. Phosphatidylserine (PS)-bearing basophilic erythroblasts and polychromatophilic erythroblasts were significantly increased in beta-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 beta-thalassaemic mice and beta-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 beta-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 beta-thalassaemia. |
