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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
A pre-existing protease is a common effector of thymocyte apoptosis mediated by diverse stimuli
H O Fearnhead1, A J Rivett, D Dinsdale
1MRC Toxicology Unit, University of Leicester, UK.
Abstract:
Data from a number of model systems support a role for proteolysis in apoptotic cell death. Using immature rat thymocytes, we demonstrate that the inhibitors N-tosyl-L-lysyl chloromethylketone (TLCK) and N-tosyl-L-phenylalanyl chloromethylketone (TPCK) have very different effects on apoptosis. TLCK inhibits apoptosis induced by diverse stimuli at an early stage prior to both DNA fragmentation and cytoplasmic changes. We show that the TLCK-sensitive target is pre-existing and not synthesized in response to apoptotic stimuli. The contrasting effects of TLCK and TPCK support the hypothesis that the TLCK target is a trypsin-like protease which is a common effector of thymocyte apoptosis.
Insights
Proteolysis inhibitors impact apoptosis differently. N-tosyl-L-lysyl chloromethylketone (TLCK) halts apoptosis early, suggesting a pre-existing trypsin-like protease is key to cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Proteolysis plays a role in apoptotic cell death.
- Specific protease inhibitors have varying effects on apoptosis.
Purpose of the Study:
- To investigate the differential effects of TLCK and TPCK on apoptosis in immature rat thymocytes.
- To identify the specific protease targeted by TLCK during apoptosis.
Main Methods:
- Treatment of immature rat thymocytes with TLCK and TPCK.
- Observation of apoptosis induction and DNA fragmentation.
- Analysis of protease activity and synthesis.
Main Results:
- TLCK significantly inhibits apoptosis induced by various stimuli at an early stage.
- TPCK shows different effects compared to TLCK.
- The TLCK-sensitive target is pre-existing, not newly synthesized.
Conclusions:
- A trypsin-like protease, sensitive to TLCK, is a crucial effector in thymocyte apoptosis.
- Differential inhibition by TLCK and TPCK supports the role of this specific protease.
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