Adaptation to Alkalosis Induces Cell Cycle Delay and Apoptosis in CD Ceils: Role of Aquaporin-2.

VALERIA RIVAROLA; PILAR FLAMENCO; LUCIANA MELAMUD; LUCIANO GALICIA; PAULA FORD; CLAUDIA CAPURRO

PUCON, CHILE

Congreso; XXIII Congresos de la Asociación Latinoamericana de Ciencias Fisiológicas (ALACF),; 2009

Collecting ducts (CD) regulate both urine concentrations, by increasing Aquaporin-2 (AQP2) expression, and acid-base status. This work aimed to examine the effects of chronic alkalosis on cell growth/death and to define whether AQP2 expression plays a role during this adaptation in renal cells. Two CD cell lines were used: WT- (not expressing AQPs) and AQP2-RCCD1 (transfected with AQP2). Our results showed that AQP2 expression per se raises cell proliferation by decreasing cell cycle length. Chronic alkalosis induced a cell proliferation reduction that began earlier and was up to 3 folds larger in AQP2-expressing cells. Cell cycle movement revealed a G2/M phase cell accumulation associated with longer S- and G2/M-transit times. This accumulation was faster and more significant in AQP2 than in WT cells. Alkaline stress also induced features of apoptosis that appeared 24 h before and were always higher in cells expressing AQP2. We conclude that in CD cells alkalosis induces a reduction in cell growth by cell cycle delay and apoptosis. The expression of the water channel AQP2 magnifies these responses probably due to an activation of mechanisms linked to cell volume regulation.