Chymotrypsin B cached in rat liver lysosomes and involved in apoptotic regulation through a mitochondrial pathway.
J Biol Chem
; 283(13): 8218-28, 2008 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-18211899
ABSTRACT
Lysosomes can trigger the mitochondrial apoptotic pathway by releasing proteases. Here we report that a 25-kDa protein purified from rat liver lysosomes possesses a long standing potent Bid cleavage activity at neutral pH, and the truncated Bid can in turn induce rapid mitochondrial release of cytochrome c. This protease was revealed as chymotrypsin B by biochemical and mass spectrometric analysis. Although it was long recognized as a digestive protease exclusively secreted by the exocrine pancreas, our data support that it also expresses and intracellularly resides in rat liver lysosomes. Translocation of lysosomal chymotrypsin B into cytosol was triggered by apoptotic stimuli such as tumor necrosis factor-alpha, and intracellular delivery of chymotrypsin B protein induced apoptotic cell death with a potency comparable with cathepsin B, suggestive of a lysosomal-mitochondrial pathway to apoptosis regulated by chymotrypsin B following its release. Noteworthily, either knockdown of chymotrypsin B expression by RNA interference or pretreatment with chymotrypsin B inhibitor N-p-tosyl-L-phenylalanine chloromethyl ketone significantly reduced tumor necrosis factor-alpha-induce apoptosis. These results demonstrate for the first time that chymotrypsin B is not only restricted to the pancreas but can function intracellularly as a pro-apoptotic protease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quimotripsina
/
Transdução de Sinais
/
Apoptose
/
Fígado
/
Lisossomos
/
Mitocôndrias
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article