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Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases
R A Jones1, V L Johnson, N R Buck
1School of Biological Sciences, University of Surrey, Guildford, England, UK.
Hepatology (Baltimore, Md.)
|June 10, 1998
Summary
Fas-induced hepatocyte apoptosis involves caspases-7 and -3 processing. Serine proteases also play a role in this apoptotic response in mouse liver cells.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Hepatocyte apoptosis is crucial for liver homeostasis.
- Fas antigen signaling is a key pathway inducing apoptosis in hepatocytes.
Purpose of the Study:
- To investigate the mechanism of Fas antigen-induced hepatocyte apoptosis.
- To identify the specific caspases and proteases involved in this process.
Main Methods:
- Induction of apoptosis in murine hepatocytes using anti-Fas monoclonal antibody.
- Assessment of apoptosis via plasma membrane blebbing, chromatin condensation, and DNA fragmentation.
- Inhibition studies using specific caspase and serine protease inhibitors.
Main Results:
- Fas-mediated apoptosis was confirmed by morphological and biochemical markers.
- Caspase inhibitors (Ac-DEVD-CHO, Z-VAD-FMK) and serine protease inhibitors (TPCK, DCI) blocked apoptosis.
- Pro-caspases-3 and -7 were processed upon Fas stimulation, with caspase-7 activation observed.
- Poly(ADP-ribose) polymerase was not degraded, suggesting specific apoptotic pathways.
Conclusions:
- Caspase processing, particularly of caspases-7 and -3, is essential for Fas-induced hepatocyte apoptosis.
- Serine proteases are implicated in the apoptotic response.
- This study elucidates key molecular players in Fas-mediated liver cell death.