Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes

Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes
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DOI:
10.1016/j.neures.2008.01.005
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发表时间:
2008-05-01
影响因子:
2.9
通讯作者:
Sobue, Kazuya
Sobue, Kazuya
中科院分区:
医学4区
文献类型:
--
作者:
Morishima, Tetsuro;Aoyama, Mineyoshi;Sobue, Kazuya

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水通道蛋白水孔蛋白(AQP)可能在大脑含水量的稳态调节以及脑水肿过程中发挥作用。脑水肿的一种可能机制是与缺血相关的乳酸性酸中毒导致的神经胶质肿胀。在此,我们研究了乳酸对培养的大鼠星形胶质细胞中AQP4表达及细胞分布的影响。孵育24小时后,35毫摩尔的乳酸使AQP4表达水平达到最大增幅。盐酸或乙酸处理也能使AQP4表达水平升高。相比之下,乳酸钠处理并未使AQP4水平升高。乳酸增加AQP4表达水平时,AQP4信使核糖核酸(mRNA)表达水平并未显著增加。在使用环己酰亚胺抑制从头合成蛋白质的条件下,乳酸仍能使AQP4表达水平升高。此外,通过细胞表面生物素化测定和免疫细胞化学检测发现,乳酸可增加星形胶质细胞表面的AQP4表达水平。乳酸诱导的星形胶质细胞膜上AQP4表达水平的增加,可能是大脑中AQP4的一种新调控机制。(c)2008爱思唯尔爱尔兰有限公司与日本神经科学学会。保留所有权利。
The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24 h of incubation, the AQP4 expression level increased maximally with 35 mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain. (c) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.