Apotransferrin induces cAMP/CREB pathway and cell cycle exit in immature oligodendroglial cells
Apotransferrin induces cAMP/CREB pathway and cell cycle exit in immature oligodendroglial cells
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DOI：
10.1002/jnr.20254
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发表时间：
2004-11-01
影响因子：
4.2
通讯作者：
Pasquini, JM
中科院分区：
文献类型：
--
作者：
Garcia, C;Paez, P;Pasquini, JM
我们以前已经证明，一个单一的颅内注射脱铁转铁蛋白（aTf）在新生大鼠增加髓鞘形成和加速分化的少突胶质细胞（OLGc）。此外，我们通过体外实验表明，从用aTf处理的4日龄大鼠（OLGc-4）分离的OLGc比对照更分化，尽管aTf对从10日龄动物（OLGc-10）分离的OLGc没有影响。在目前的工作中，我们分析了第二信使的作用，在影响的aTf对OLGc的成熟在不同的发展阶段。我们使用Percoll密度梯度从大鼠脑中分离OLGc-4和OLGc-10，并用aTf脉冲短暂处理细胞，或在存在或不存在aTf的情况下将其培养2天。在OLGc-4中，aTf短脉冲后，cAMP（cAMP）水平、cAMP反应元件结合蛋白（CREB）磷酸化和cAMP反应转录因子的DNA结合能力增加。用aTf处理OLGc-4减少了溴脱氧尿苷（BrdU）掺入，并改变了p27和细胞周期蛋白D1的水平。这种糖蛋白似乎仅在发育的早期阶段通过cAMP途径作用于OLGc，并作用于某些敏感的细胞群体，加速其分化，这可能是过早退出细胞周期的结果。(C)2004 Wiley-Liss，Inc.
We have demonstrated previously that a single intracranial injection of apotransferrin (aTf) in neonatal rats increases myelination and accelerates differentiation of oligodendroglial cells (OLGc). In addition, we have shown through in vitro experiments that OLGc isolated from 4-day-old rats (OLGc-4) treated with aTf were more differentiated than were controls although aTf had no effect upon OLGc isolated from 10-day-old animals (OLGc-10). In the present work, we analyzed the role of second messengers in the effect of aTf upon the maturation of OLGc at different stages of development. We isolated OLGc-4 and OLGc-10 from rat brain using a Percoll density gradient and briefly treated the cells with a pulse of aTf or kept them in culture during 2 days in the presence or absence of aTf. In OLGc-4, after a short pulse of aTf, there was an increase in the levels of cyclic AMP (cAMP), in the phosphorylation of cAMP response element-binding protein (CREB) and in the DNA-binding capacity of cAMP-responsive transcription factors. Treatment of OLGc-4 with aTf diminished bromodeoxyuridine (BrdU) incorporation and changed levels of p27 and cyclin D1. This glycoprotein seemed to act on OLGc through the cAMP pathway only at early stages of development and on a certain sensitive cell population, accelerating their differentiation, probably as a consequence of premature withdrawal from the cell cycle. (C) 2004 Wiley-Liss, Inc.