Arima Hajime, Yamamoto Naoki, Sobue Kazuya, Umenishi Fuminori, Tada Toyohiro, Katsuya Hirotada, Asai Kiyofumi
Department of Anesthesia and Critical Care, Okazaki City Hospital, 3-1 Goshoai, Koryuji-cho, Okazaki 444-8553, Japan.
J Biol Chem. 2003 Nov 7;278(45):44525-34. doi: 10.1074/jbc.M304368200. Epub 2003 Aug 27.
The membrane pore proteins, aquaporins (AQPs), facilitate the osmotically driven passage of water and, in some instances, small solutes. Under hyperosmotic conditions, the expression of some AQPs changes, and some studies have shown that the expression of AQP1 and AQP5 is regulated by MAPKs. However, the mechanisms regulating the expression of AQP4 and AQP9 induced by hyperosmotic stress are poorly understood. In this study, we observed that hyperosmotic stress induced by mannitol increased the expression of AQP4 and AQP9 in cultured rat astrocytes, and intraperitoneal infusion of mannitol increased AQP4 and AQP9 in the rat brain cortex. In addition, a p38 MAPK inhibitor, but not ERK and JNK inhibitors, suppressed their expression in cultured astrocytes. AQPs play important roles in maintaining brain homeostasis. The expression of AQP4 and AQP9 in astrocytes changes after brain ischemia or traumatic injury, and some studies have shown that p38 MAPK in astrocytes is activated under similar conditions. Since mannitol is commonly used to reduce brain edema, understanding the regulation of AQPs and p38 MAPK in astrocytes under hyperosmotic conditions induced with mannitol may lead to a control of water movements and a new treatment for brain edema.
膜孔蛋白水通道蛋白（AQPs）促进水以及在某些情况下小分子溶质的渗透驱动转运。在高渗条件下，一些水通道蛋白的表达会发生变化，并且一些研究表明，水通道蛋白1（AQP1）和水通道蛋白5（AQP5）的表达受丝裂原活化蛋白激酶（MAPKs）调控。然而，高渗应激诱导水通道蛋白4（AQP4）和水通道蛋白9（AQP9）表达的调控机制尚不清楚。在本研究中，我们观察到甘露醇诱导的高渗应激增加了培养的大鼠星形胶质细胞中AQP4和AQP9的表达，并且腹腔注射甘露醇增加了大鼠脑皮质中AQP4和AQP9的表达。此外，p38丝裂原活化蛋白激酶抑制剂而非细胞外信号调节激酶（ERK）和应激活化蛋白激酶（JNK）抑制剂可抑制其在培养的星形胶质细胞中的表达。水通道蛋白在维持脑内稳态中发挥重要作用。脑缺血或创伤性损伤后星形胶质细胞中AQP4和AQP9的表达会发生变化，并且一些研究表明，在类似条件下星形胶质细胞中的p38丝裂原活化蛋白激酶会被激活。由于甘露醇常用于减轻脑水肿，了解甘露醇诱导的高渗条件下星形胶质细胞中水通道蛋白和p38丝裂原活化蛋白激酶的调控机制可能会实现对水转运的控制并为脑水肿带来新的治疗方法。
