Regulation of aquaporin-4 expression in astrocytes

Aquaporin-4 (AQP4), a mercury-insensitive water channel protein. is abundan t in the central nervous system and is localized in astrocytes and ependyma l cells. AQP4 is speculated to maintain the homeostasis of intracellular an d extracellular water in the brain, but little is known about the mechanism of induction of its expression. To investigate the expressional regulation of AQP4, we analyzed changes in its expression during chemically induced d ifferentiation of embryonal carcinoma cells (P19) to neuronal and astrocyti c cells, and during the cell cycle of glioma cells. After exposure to retin oic acid for 4 days AQP4 mRNA expression started at the initiation of astro cytic differentiation of P19 cells at 6 days, and increased markedly by 21 days. AQP4 expression was parallel to that of GFAP, a marker intermediate f ilament of astrocytes. In glioma cell lines, AQP4 mRNA was not detected in the growing phase, but was induced when the cell cycle was arrested at G0/G 1 by transient expression of p21. Although quiescent astrocytes in the G0/G 1-phase cultured under the serum-free condition exhibited a high expression of AQP4. serum supplement moved them to the S-phase and markedly decreased the AQP expression. These results suggest that AQP4 expression may be indu ced not only at the initiation of astrocytic differentiation of neural stem cells, but also at the G0/G1-phase during the cell cycle of astrocytes. (C ) 2001 Elsevier Science B.V. All rights reserved.