Dinitrosyl iron complexes with thiol-containing ligands and S-nitroso-D,L-penicillamine as inductors of heat shock protein synthesis in H35 hepatoma cells

The concentration-dependent effect of various nitric oxide donors on synthe sis of different heat shock proteins was evaluated in Reuber H35 hepatoma c ells and their heat shock protein-inducing ability was compared with the ef fect of a heat shock. A 6 h incubation of H35 cells with the dimeric (diama gnetic) form of dinitrosyl iron complex with glutathione or N-acetyl-L-cyst eine activated synthesis of various heat shock proteins, heat shock protein 28, 32, 60, 70, 90 and 100, Synthesis of these proteins was evaluated by [ S-35]methionine and [S-35]cysteine labelling with subsequent separation of proteins by polyacrylamide gel electrophoresis, The dinitrosyl iron complex with glutathione appeared to be the most efficient inductor of heat shock protein synthesis and initiated the synthesis of heat shock protein 28 even more efficiently than a 30 min heating of cells. In the same experiments, S-nitroso-D,L-penicillamine exerted a considerably lesser effect on the syn thesis of heat shock proteins. It was suggested that the active moiety of d initrosyl iron complexes as inductors of heat shock protein synthesis is re presented by their Fe+(NO+)(2) groups which move to thiol groups of the pro teins participating in the initiation of heat shock protein synthesis, (C) 1999 Federation of European Biochemical Societies.