Di Giacomo V, Sancilio S, Caravatta L, Rana R A, Di Pietro R, Cataldi A
Dipartimento di Biomorfologia, Università G. d'Annunzio, Chieti-Pescara, Italy.
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):679-88. doi: 10.1177/039463200902200313.
Among the molecular events underlying erythroid differentiation, we analyzed the signalling pathway leading to cAMP response element binding (CREB) nuclear transcription factor activation. Normal donor blood light density cells differentiated to pro-erythroblasts during the proliferative phase (10 days) of the human erythroblast massive amplification (HEMA) culture, and to orthochromatic erythroblasts, during the differentiation phase (4 additional days) of the culture. Since erythropoietin was present all over the culture, also pro-erythroblasts left in proliferative medium for 14 days continued their maturation without reaching the final steps of differentiation. p38 mitogen activated protein kinase (p38 MAPK) and CREB maximal activation occurred upon 4 days of differentiation induction, whereas a lower activation was detectable in the cells maintained in parallel in proliferative medium (14 days). Interestingly, when SB203580, a specific p38 MAPK inhibitor, was added to the culture the percentage of differentiated cells decreased along with p38 MAPK and CREB phosphorylation. All in all, our results evidence a role for p38 MAPK in activating CREB metabolic pathway in the events leading to erythroid differentiation.
在红系分化的分子事件中，我们分析了导致环磷酸腺苷反应元件结合（CREB）核转录因子激活的信号通路。在人类成红细胞大规模扩增（HEMA）培养的增殖期（10天），正常供体血液低密度细胞分化为早幼红细胞，在培养的分化期（额外4天）分化为正染红细胞。由于整个培养过程中都存在促红细胞生成素，因此留在增殖培养基中14天的早幼红细胞也能继续成熟，但未达到分化的最后阶段。p38丝裂原活化蛋白激酶（p38 MAPK）和CREB的最大激活发生在诱导分化4天后，而在平行于增殖培养基中培养14天的细胞中可检测到较低的激活水平。有趣的是，当向培养物中添加特异性p38 MAPK抑制剂SB203580时，分化细胞的百分比随着p38 MAPK和CREB磷酸化而降低。总而言之，我们的结果证明p38 MAPK在导致红系分化的事件中激活CREB代谢途径方面发挥作用。
