Heat shock proteins and the cellular response to osmotic stress

In antidiuresis, the intrarenal distribution of HSP25/27, alpha beta -cryst allin, HSP72, OSP94 and HSP110 corresponds to the osmotic gradient between cortex and papilla: low amounts in the cortex and high values in the inner medulla and papilla. In addition, medullary HSP72 levels change appropriate ly with the diuretic state. Studies on MUCK cells suggest that, in the rena l medulla in vivo, stressors, such as NaCl and low pH, may act in concert t o induce HSP72 expression. Urea, added to the medium at high concentrations (600 mM), causes the majority of MUCK cells to die. Prior exposure of thes e cells to hypertonic media (NaCl addition), a maneuver that induces HSP72, protects the cells against the deleterious effects of high urea concentrat ions. Inhibition of HSP72 expression by stable antisense transfection or SB 203580 treatment abolishes the beneficial effects of prior hypertonic stres s. Conversely, overexpression of HSP72 under isotonic conditions by a dexam ethasone-driven vector confers substantial resistance against subsequent ex posure to high urea concentrations. Taken together these results suggest th at also in the renal inner medulla, NaCl-induced enhancement of HSP72 expre ssion may help counteract the detrimental effects of high urea concentratio ns. Copyright (C) 2000 S. Karger AG Basel.