ADVANCED GLYCATION ENDPRODUCTS STIMULATE THE MAP-KINASE PATHWAY IN TUBULUS CELL-LINE LLC-PK1

Advanced glycation endproducts (AGEs) are suggested to play an importa nt role in diabetic nephropathy, They induce specific cellular respons es such as the release of cytokines in different cell lines, The effec t of AGEs on signal transduction pathways was investigated in the rena l tubulus cell line LLC-PK1, Using a serine-phosphate-specific antibod y AGE-induced cellular responses associated with phosphorylation/depho sphorylation events were demonstrated, In particular, the p42(MAP) kin ase and its downstream target, the AP-I complex, are shown to be activ ated by AGE-BSA but not by BSA. In contrast, only partial phosphorylat ion is observed for the p70(S6)-kinase, Thus, AGEs appear to induce sp ecific signal transduction pathways. (C) 1997 Federation of European B iochemical Societies.