Urea protects Caenorhabditis elegans against hypertonic stress: a genetic model for cellular responses to urea? (1099.7)

Urea is a cell‐permeable nitrogenous waste product that denatures macromolecules and causes cellular stress at high concentrations. However, urea accumulates in the mammalian renal medulla as a part of the urine concentrating mechanism and in elasmobranch fish to balance the high osmolarity of seawater. Although high concentrations of urea can be detrimental, pre‐exposure of mammalian cells to moderate concentrations promotes resistance to high concentrations of the impermeable osmolyte NaCl in addition to high urea. Although the mechanisms of this conditioning are poorly defined, studies to date indicate that they are largely distinct from pathways activated by high levels of NaCl. The nematode Caenorhabditis elegans can tolerate extremely high levels of NaCl and other impermeable osmolytes in part by accumulating the organic osmolyte glycerol and by modulating protein translation. Here, we conducted a series of experiments investigating the effects of urea in C. elegans to determine if this genetically tractable system might be useful for defining protective mechanisms. We find that C. elegans can tolerate extremely high levels of urea (~600 mM) and that pre‐exposure to moderate urea promotes resistance to high urea and high NaCl. Therefore, the general protective effects of moderate urea levels appear to be highly conserved and therefore amenable to genetic analysis in C. elegans. Our ongoing studies include determining if the mechanisms of urea protection in C. elegans are distinct from those initiated by NaCl. Grant Funding Source : NSF Grant IOS1120130 to KPC