Hermine O, Arlet J-B, Ribeil J-A, Guillerm F, Vandekerkhove J, Courtois G
CNRS UMR 8143, labex des globules rouges GR-ex, hôpital Necker, institut Imagine, université Sorbonne Paris Cité, Paris Descartes, Paris, France.
Transfus Clin Biol. 2013 May;20(2):144-7. doi: 10.1016/j.tracli.2013.03.005. Epub 2013 May 2.
Erythropoiesis is finely regulated by two major cytokines, stem cell factor (SCF) and erythropoietin (Epo). Decrease levels of Epo result in caspase activation and erythroid progenitors apoptosis. However, normal erythroid cell maturation requests caspase activation and cleavage of various caspase substrates, except the erythroid transcription factor GATA-1, that is protected by interaction with the chaperone HSP70 in the nucleus. Therefore, molecular abnormalities associated with decrease of HSP70 expression in the nucleus may result in ineffective erythropoiesis characterized by apoptosis and impaired maturation of erythroid precursors. These findings open new potential targeted therapies for erythroid disorders.
红细胞生成受到两种主要细胞因子的精细调控,即干细胞因子(SCF)和促红细胞生成素(Epo)。Epo水平降低会导致半胱天冬酶激活和红系祖细胞凋亡。然而,正常的红系细胞成熟需要半胱天冬酶激活并切割各种半胱天冬酶底物,但红系转录因子GATA-1除外,它在细胞核中通过与伴侣蛋白HSP70相互作用而受到保护。因此,与细胞核中HSP70表达降低相关的分子异常可能导致以红系前体细胞凋亡和成熟受损为特征的无效红细胞生成。这些发现为红系疾病开辟了新的潜在靶向治疗方法。