Related Experiment Videos
Tissue transglutaminase differentially modulates apoptosis in a stimuli-dependent manner
Janusz Tucholski1, Gail V W Johnson
1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 1720 7th Avenue South, SC 1061, Birmingham, AL 35294-0017, USA.
Journal of Neurochemistry
|June 18, 2002
Summary
Tissue transglutaminase (tTG) has a dual role in apoptosis. It promotes cell death when its activity increases but protects cells when its activity is unchanged, depending on the stressor.
Area of Science:
- Cell Biology
- Biochemistry
- Apoptosis Research
Background:
- Tissue transglutaminase (tTG) is known for its transamidating activity and interactions with nucleotides.
- Its role in apoptosis is debated, with conflicting evidence regarding its pro-apoptotic function.
Purpose of the Study:
- To investigate the specific role of tissue transglutaminase (tTG) in apoptosis.
- To determine if tTG's transamidating activity is essential for its function in the apoptotic process.
Main Methods:
- Human neuroblastoma SH-SY5Y cells were stably transfected to express vector only (SH/pcDNA), wild-type tTG (SH/tTG), or a catalytically inactive mutant (SH/C277S).
- Cells were subjected to three apoptotic stimuli: osmotic stress, staurosporine treatment, and heat shock.
- Caspase-3 activity, LDH release, and apoptotic nuclear changes were measured.
Main Results:
- In response to osmotic stress and staurosporine, SH/tTG cells showed increased caspase-3 activation and apoptosis, correlating with heightened tTG transamidating activity.
- Under heat shock, where tTG activity did not increase, both SH/tTG and SH/C277S cells exhibited reduced caspase-3 activity and apoptosis compared to controls.
- These effects were independent of the PI3K/Akt and ERK pathways.
Conclusions:
- The impact of tissue transglutaminase (tTG) on apoptosis is stimulus-dependent.
- tTG facilitates apoptosis when its transamidating activity is upregulated by the stressor.
- tTG can inhibit apoptosis via a non-transamidating mechanism when its activity is not enhanced by the stressor.