Anserine and Carnosine Induce HSP70-Dependent H 2 S Formation in Endothelial Cells and Murine Kidney.

Anserine and carnosine have nephroprotective actions; hydrogen sulfide (HS) protects from ischemic tissue damage, and the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions of both dipeptides with HS. HS formation was measured in human proximal tubular epithelial cells (HK-2); three endothelial cell lines (HUVEC, HUAEC, MCEC); and in renal murine tissue of wild-type (WT), carnosinase-1 knockout -KO) and -KO mice. Diabetes was induced by streptozocin. Incubation with carnosine increased HS synthesis capacity in tubular cells, as well as with anserine in all three endothelial cell lines. HS dose-dependently reduced anserine/carnosine degradation rate by serum and recombinant carnosinase-1 (CN1). Endothelial -KO reduced HS formation and abolished the stimulation by anserine and could be restored by transfection. In female -KO mice, kidney HS formation was halved. In -KO mice, kidney anserine concentrations were several-fold and sex-specifically increased. Kidney HS formation capacity was increased 2-3-fold in female mice and correlated with anserine and carnosine concentrations. In diabetic -KO mice, renal anserine and carnosine concentrations as well as HS formation capacity were markedly reduced compared to non-diabetic -KO littermates. Anserine and carnosine induce HS formation in a cell-type and Hsp70-specific manner within a positive feedback loop with CN1.