Present address: Faculty of Biology, University of Barcelona, Diagonal, 645, 08028 Barcelona, Spain.
Altered apoptotic responses in neurons lacking RhoB GTPase
Article first published online: 18 NOV 2011
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 34, Issue 11, pages 1737–1746, December 2011
How to Cite
Barberan, S., McNair, K., Iqbal, K., Smith, N. C., Prendergast, G. C., Stone, T. W., Cobb, S. R. and Morris, B. J. (2011), Altered apoptotic responses in neurons lacking RhoB GTPase. European Journal of Neuroscience, 34: 1737–1746. doi: 10.1111/j.1460-9568.2011.07891.x
- Issue published online: 28 NOV 2011
- Article first published online: 18 NOV 2011
- Received 9 March 2011, revised 11 August 2011; accepted 2 September 2011
- Rho GTPase;
Caspase 3 activation has been linked to the acute neurotoxic effects of central nervous system damage, as in traumatic brain injury or cerebral ischaemia, and also to the early events leading to long-term neurodegeneration, as in Alzheimer’s disease. However, the precise mechanisms activating caspase 3 in neuronal injury are unclear. RhoB is a member of the Rho GTPase family that is dramatically induced by cerebral ischaemia or neurotrauma, both in preclinical models and clinically. In the current study, we tested the hypothesis that RhoB might directly modulate caspase 3 activity and apoptotic or necrotic responses in neurons. Over-expression of RhoB in the NG108-15 neuronal cell line or in cultured corticohippocampal neurons elevated caspase 3 activity without inducing overt toxicity. Cultured corticohippocampal neurons from RhoB knockout mice did not show any differences in sensitivity to a necrotic stimulus – acute calcium ionophore exposure – compared with neurons from wild-type mice. However, corticohippocampal neurons lacking RhoB exhibited a reduction in the degree of DNA fragmentation and caspase 3 activation induced by the apoptotic agent staurosporine, in parallel with increased neuronal survival. Staurosporine induction of caspase 9 activity was also suppressed. RhoB knockout mice showed reduced basal levels of caspase 3 activity in the adult brain. These data directly implicate neuronal RhoB in caspase 3 activation and the initial stages of programmed cell death, and suggest that RhoB may represent an attractive target for therapeutic intervention in conditions involving elevated caspase 3 activity in the central nervous system.