Hyperosmolar mannitol stimulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes
Hyperosmolar mannitol stimulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes
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DOI：
10.1074/jbc.m304368200
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发表时间：
2003-11-07
影响因子：
4.8
通讯作者：
Asai, K
中科院分区：
文献类型：
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作者：
Arima, H;Yamamoto, N;Asai, K
膜孔蛋白水通道蛋白 (AQP) 促进水的渗透驱动通过，在某些情况下还促进小溶质的通过。高渗条件下，部分AQPs的表达发生变化，有研究表明AQP1和AQP5的表达受到MAPKs的调节。然而，高渗应激诱导的 AQP4 和 AQP9 表达调节机制尚不清楚。在这项研究中，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，腹腔注射甘露醇增加了大鼠大脑皮层中AQP4和AQP9的表达。此外，p38 MAPK 抑制剂（而非 ERK 和 JNK 抑制剂）抑制了它们在培养的星形胶质细胞中的表达。 AQP 在维持大脑稳态方面发挥着重要作用。脑缺血或创伤性损伤后星形胶质细胞中AQP4和AQP9的表达发生变化，有研究表明星形胶质细胞中的p38 MAPK在类似条件下被激活。由于甘露醇通常用于减轻脑水肿，了解甘露醇诱导的高渗条件下星形胶质细胞中 AQP 和 p38 MAPK 的调节可能会导致水运动的控制和脑水肿的新治疗。
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.