Lineage-specific modulation of calcium pump expression during myeloid differentiation
Lineage-specific modulation of calcium pump expression during myeloid differentiation
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DOI：
10.1182/blood.v93.12.4395.412k06_4395_4405
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发表时间：
1999-06-15
期刊：
影响因子：
20.3
通讯作者：
Papp, B
中科院分区：
文献类型：
--
作者：
Launay, S;Giannì, M;Papp, B
钙通过肌质内质网钙转运ATP酶（SERCA）从胞质溶胶积累到内质网中。由于钙储存在内质网是必不可少的细胞生长，分化，钙信号，和凋亡，因为不同的SERCA酶具有不同的功能特性，在本报告中，我们探讨了SERCA表达在体外分化的人髓细胞/早幼粒细胞系HL-60和NB 4和新鲜分离的急性早幼粒细胞白血病细胞。已发现两种SERCA种类在这些细胞中共表达：SERCA 2b和另一种亚型SERCA（PLIM），其被PLIM 430单克隆抗体识别。全反式视黄酸或环AMP类似物沿中性粒细胞谱系诱导分化沿着导致SERCA（PLIM）表达增加，而SERCA 2b亚型的表达降低。SERCA表达的调节在mRNA水平上也是明显的。维甲酸受体亚型特异性类维生素A的实验表明，SERCA的表达是由维甲酸受体铜依赖性信号调节。视黄酸抗性细胞变体的SERCA表达对治疗是难治的。分化沿着单核细胞/巨噬细胞谱系佛波酯导致两个SERCA亚型的表达增加。此外，当在糖皮质激素地塞米松（一种已知的单核细胞分化抑制剂）存在下用佛波酯处理细胞时，观察到选择性阻断SERCA（PLIM）的诱导。改变的SERCA表达改变了钙转运到内质网中的功能特征。这些观察结果首次表明，钙泵表达的调制是髓样前体细胞分化程序的一个组成部分，并表明在细胞成熟过程中发生内质网的谱系特异性重塑。此外，这些数据表明，SERCA亚型可能作为有用的标记物的髓系分化的研究。(C)1999年，美国血液学会。
Calcium is accumulated from the cytosol into the endoplasmic reticulum by sarco-endoplasmic reticulum calcium transport ATPase (SERCA) enzymes. Because calcium stored in the endoplasmic reticulum is essential for cell growth, differentiation, calcium signaling, and apoptosis and because different SERCA enzymes possess distinct functional characteristics, in the present report we explored SERCA expression during in vitro differentiation of the human myeloid/promyelocytic cell lines HL-60 and NB4 and of freshly isolated acute promyelocytic leukemia cells. Two SERCA species have been found to be coexpressed in these cells: SERCA 2b and another isoform, SERCA(PLIM), which is recognized by the PLIM430 monoclonal antibody, Induction of differentiation along the neutrophil granulocytic lineage by all-trans retinoic acid or cyclic AMP analogs led to an increased expression of SERCA(PLIM), whereas the expression of the SERCA 2b isoform was decreased. The modulation of SERCA expression was manifest also on the mRNA level. Experiments with retinoic acid receptor isoform-specific retinoids indicated that SERCA expression is modulated by retinoic acid receptor cu-dependent signaling. SERCA expression of retinoic acid-resistant cell variants was refractory to treatment. Differentiation along the monocyte/macrophage lineage by phorbol ester resulted in an increased expression of both SERCA isoforms. In addition, when cells were treated by phorbol ester in the presence of the glucocorticoid dexamethasone, a known inhibitor of monocyte differentiation, a selective blockage of the induction of SERCA(PLIM) was observed, Altered SERCA expression modified the functional characteristics of calcium transport into the endoplasmic reticulum. These observations show for the first time that the modulation of calcium pump expression is an integral component of the differentiation program of myeloid precursors and indicate that a lineage-specific remodelling of the endoplasmic reticulum occurs during cell maturation. In addition, these data show that SERCA isoforms may serve as useful markers for the study of myeloid differentiation. (C) 1999 by The American Society of Hematology.