Morishima Tetsuro, Aoyama Mineyoshi, Iida Yuko, Yamamoto Naoki, Hirate Hiroyuki, Arima Hajime, Fujita Yoshihito, Sasano Hiroshi, Tsuda Takako, Katsuya Hirotada, Asai Kiyofumi, Sobue Kazuya
Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
Neurosci Res. 2008 May;61(1):18-26. doi: 10.1016/j.neures.2008.01.005. Epub 2008 Jan 17.
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 24h of incubation, the AQP4 expression level increased maximally with 35mM 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.
水通道蛋白水孔蛋白（AQP）可能在脑内水分含量的稳态及脑水肿中发挥作用。脑水肿的一种可能机制是与缺血相关的乳酸酸中毒导致神经胶质细胞肿胀。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，35mM乳酸使AQP4表达水平达到最大程度升高。盐酸或乙酸也使AQP4表达水平升高。相比之下，乳酸钠未使AQP4水平升高。乳酸使AQP4表达水平升高，但AQP4 mRNA表达水平无显著增加。在用放线菌酮抑制从头合成蛋白质的条件下，乳酸仍使AQP4表达水平升高。此外，通过细胞表面生物素化分析和免疫细胞化学检查确定，乳酸增加了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表达水平升高可能是脑内AQP4的一种新调节机制。
