Urea protects from the proapoptotic effect of NaCl in renal medullary cells

Hypertonic NaCl upregulated two sensitive and specific biochemical indices of apoptosis, caspase-3 activation and annexin V binding, in a time- and do se-dependent fashion in renal medullary mIMCD3 cells. Pretreatment with ure a (200 mM for 30 min) protected from the proapoptotic effect of hypertonic stress (200 mosmol/kgH(2)O) in this model. The protective effect of urea wa s dose dependent and was effective even when applied a short time (less tha n or equal to 1 h) following NaCl exposure; this protective effect was not observed in the nonrenal 3T3 cell line. In both mIMCD3 and 3T3 cells, urea failed to protect from the proapoptotic stressor, ultraviolet (UV)-B irradi ation. The ability of urea to protect from hypertonic stress was approximat ely comparable to the protective effect of peptide mitogens epidermal growt h factor and insulin-like growth factor (IGF), but it potentiated the IGF e ffect. Interestingly, the tyrosine kinase inhibitor, genistein, potentiated the proapoptotic effect of urea yet abrogated the proapoptotic effect of h ypertonic stress. In aggregate, these data indicate that urea protects from the proapoptotic effect of hypertonic stress in a potentially cell type-sp ecific and stimulus-specific fashion.