Catechin derivatives: specific inhibitor for caspases-3, 7 and 2, and the prevention of apoptosis at the cell and animal levels.
Tea-catechin derivatives are shown to inhibit activities of caspases-3, 2 and 7 in vitro, and prevented experimental apoptosis at the cell and animal levels. Epigallo-catechin-gallate showed the strongest inhibition at 1 x 10(-7)M to these caspases, but cysteine cathepsins and caspase-8 were not inhibited. Caspase-3 inhibition showed a 2nd-order allosteric-type, but the inhibition of caspases-2 and 7 showed a non-competitive-type. The apoptosis-test using cultured HeLa cells was inhibited by these catechins. In rat hepatocytes, apoptosis was induced by d-galactosamine in vivo. In this case, caspase-3 activity in the cytoplasm, the serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were effects, and these elevations were suppressed by administration of catechin.
Katunuma
Nobuhiko
N
Tokushima Bunri University, Institute for Health Sciences, 180 Nishihamabouji, Tokushima 770-8514, Japan. katunuma@tokushima.bunri-u.ac.jp
Ohashi
Atsushi
A
Sano
Etsuko
E
Ishimaru
Naozumi
N
Hayashi
Yoshio
Y
Murata
Etsuko
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2; D053148:Caspase 3; D053179:Caspase 7; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002474:Cell-Free System / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005688:Galactosamine / Q000008:administration & dosage / Q000633:toxicity; D006367:HeLa Cells; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D051381:Rats
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005688:Galactosamine; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C505410:Casp3 protein, rat; D053143:Caspase 2; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases