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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
Altered apoptotic responses in neurons lacking RhoB GTPase
Sara Barberan1, Kara McNair, Khalil Iqbal
1Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
The European Journal of Neuroscience
|November 22, 2011
Summary
Neuronal RhoB directly activates caspase 3, a key enzyme in programmed cell death. This finding suggests RhoB as a potential therapeutic target for central nervous system injuries and neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Caspase 3 activation is implicated in acute central nervous system (CNS) damage and long-term neurodegeneration.
- Mechanisms of caspase 3 activation in neuronal injury remain unclear.
- RhoB, a Rho GTPase, is significantly induced by CNS injury.
Purpose of the Study:
- To investigate the role of RhoB in modulating caspase 3 activity and neuronal death pathways.
- To test the hypothesis that RhoB directly influences caspase 3 activation and apoptotic/necrotic responses.
Main Methods:
- Over-expression of RhoB in neuronal cell lines and primary cultures.
- Utilizing RhoB knockout mice and wild-type littermates.
- Assessing caspase 3 and caspase 9 activity, DNA fragmentation, and neuronal survival following apoptotic and necrotic stimuli.
Main Results:
- RhoB over-expression elevated caspase 3 activity in neurons without causing toxicity.
- Neurons lacking RhoB showed reduced DNA fragmentation and caspase 3 activation upon apoptotic stimulation (staurosporine).
- RhoB deficiency led to increased neuronal survival and suppressed staurosporine-induced caspase 9 activity, with reduced basal caspase 3 activity in knockout brains.
Conclusions:
- Neuronal RhoB directly implicates in caspase 3 activation and the initiation of programmed cell death.
- RhoB plays a role in apoptotic, but not necrotic, neuronal death pathways.
- RhoB emerges as a potential therapeutic target for CNS conditions characterized by elevated caspase 3 activity.
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