Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes

P. Kwo, T. Patel, S. F. Bronk, G. J. Gores

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Glycodeoxycholate (GDC) induces apoptosis in hepatocytes by a mechanism associated with DNA cleavage by endonucleases. In many models of apoptosis, proteolysis is required prior to DNA cleavage. Our aims were to determine if enhanced proteolysis is a mechanism causing GDC-mediated apoptosis. In cultured rat hepatocytes exposed to 50 μM GDC for 4 h, nonlysosomal proteolysis increased by 65% compared with controls. The serine protease inhibitor Na-p-tosyl-L-lysine chloromethyl ketone (TLCK; 100 μM) reduced cell death from apoptosis by 75% after 4 h of treatment with GDC. TLCK also inhibited DNA fragmentation. There was a twofold increase in nuclear serinelike protease activity during GDC-induced apoptosis accompanied by a 2.5-fold reduction in nonnuclear serine protease activity, suggesting translocation of the protease from the cytosol to the nucleus. Zn2+, an inhibitor of apoptosis, also inhibited nonlysosomal proteolysis and nuclear serinelike protease activity. These novel data suggest that nonlysosomal serinelike protease activity contributes to hepatocyte apoptosis. These data may be important in understanding apoptosis in other cell types and in providing insight into the mechanisms of liver injury during cholestasis.

Original languageEnglish (US)
Pages (from-to)G613-G621
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number4 31-4
StatePublished - 1995


  • acridine orange
  • bile salts
  • cholestasis
  • deoxyribonucleic acid fragmentation
  • endonucleases
  • nuclear proteases
  • protease inhibitors
  • serine proteases
  • zinc

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


Dive into the research topics of 'Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes'. Together they form a unique fingerprint.

Cite this