A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by d-galactosamine

A new apoptosis cascade mediated by lysosomal lactoferrin was found in apoptotic liver induced by d-galactosamine. Caspase-3 and lactoferrin were increased in the apoptotic liver cytoplasm and serum transaminases were elevated. Recombinant lactoferrin stimulated procaspase-3 processing at 10−6–10−7 M to an extent similar to that by granzyme B in vitro. Lactoferrin changed procaspase-3 structure susceptible to the processing. Synthetic peptide Y679-K695 in lactoferrin molecule inhibited the processing of procaspase-3 by lactoferrin. Lactoferrin in lysosomes was decreased and lactoferrin released into cytoplasm was increased quantitatively in d-galactosamine induced apoptotic liver, and procaspase-3 in cytoplasm was processed to caspase-3.