Increased aquaporin-4 expression in ammonia-treated cultured astrocytes

Brain edema is a serious complication of hepatic encephalopathy associated with fulminant hepatic failure (FHF). Factors responsible for such swelling are not clear, but ammonia, a toxin strongly implicated in FHF, is known to induce astrocyte swelling. The mechanism(s) responsible for ammonia-induced swelling, however, are not known. Aquaporins are plasma membrane proteins that mediate transmembrane water movement. To investigate the potential role of aquaporins in astrocyte swelling, we measured aquaporin-4 (AQP-4) protein expression in cultured astrocytes exposed to 5 mM NH4Cl. AQP-4 levels significantly increased 10 h after treatment with ammonia, and displayed a progressive rise up to 48 h, which appeared to precede the onset of astrocyte swelling. AQP-4 may be involved in the astrocyte swelling associated with hyperammonemic states.