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 Y(679)-K(695) 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.
Katunuma
Nobuhiko
N
Institute for Health Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-cho, Tokushima 770-8514, Japan. katunuma@tokushima.bunri-u.ac.jp
Le
Quang Trong
QT
Murata
Etsuko
E
Matsui
Atsushi
A
Majima
Eiji
E
Ishimaru
Naozumi
N
Hayashi
Yoshio
Y
Ohashi
Atsushi
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005688:Galactosamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry*; D051379:Mice; D008970:Molecular Weight; D051381:Rats
D005688:Galactosamine; D007781:Lactoferrin; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases