GROWTH-CONTROL OR TERMINAL DIFFERENTIATION - ENDOGENOUS PRODUCTION AND DIFFERENTIAL ACTIVITIES OF VITAMIN A METABOLITES IN HL-60 CELLS
GROWTH-CONTROL OR TERMINAL DIFFERENTIATION - ENDOGENOUS PRODUCTION AND DIFFERENTIAL ACTIVITIES OF VITAMIN A METABOLITES IN HL-60 CELLS
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DOI：
10.1084/jem.178.6.1995
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发表时间：
1993-12-01
影响因子：
15.3
通讯作者：
HAMMERLING, U
中科院分区：
文献类型：
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作者：
EPPINGER, TM;BUCK, J;HAMMERLING, U
维生素A（视黄醇）是一种原激素，转化为多种代谢产物后发挥其多效生物学效应。在这篇报告中，我们描述了三种内源性视黄醇衍生的效应分子，14-羟基反转录视黄醇（14-HRR），无氢视黄醇（AR）和视黄酸（RA）的鉴定，以及视黄醇的一种推定储存形式，视黄醇酯（R-E）在人早幼粒细胞白血病细胞系HL-60中。将视黄醇代谢物外源应用于缺乏视黄醇的无血清HL-60培养物中，可以鉴定每种代谢物的独特细胞功能：14-HRR是HL-60的生长因子。AR是14-HRR的功能性拮抗剂，具有生长抑制活性，RA是粒细胞分化伴随生长停滞的有效诱导剂。最后，当没有外部视黄醇可用时，细胞内R-E作为存储形式允许持续生产14-HRR。
Vitamin A (retinol) is a prohormone that exerts its pleiotropic biological effects after conversion into multiple metabolites. In this report we describe the identification of three endogenous, retinol-derived effector molecules, 14-hydroxy-retro-retinol (14-HRR), anhydroretinol (AR), and retinoic acid (RA) and a putative storage form of retinol, retinylesters (R-E) in the human promyelocytic leukemia cell line HL-60. Exogenous application of the retinol metabolites in retinol-depleted serum-free cultures of HL-60 allowed the identification of unique cellular functions for each metabolite: 14-HRR is a growth factor for HL-60. AR is a functional antagonist of 14-HRR with growth-inhibiting activity, and RA is a potent inducer of granulocyte differentiation accompanied by growth arrest. Finally, intracellular R-E serves as storage form allowing continuous production of 14-HRR when no external retinol is available.