Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 6
Contribution of RhoGTPases to calcium dependent activation of p38 and excitotoxic cell
death
Jiong Cao, Maria M. Semenova, Anu M.J. Mäki-Hokkonen and Michael J. Courtney/
Molecular Signalling Lab, A. I. Virtanen Institute, University of Kuopio, Kuopio FIN
70211, Finland. E-mail : courtney@messi.uku.fi /
Excitotoxic neuronal death contributes to many neurological disorders. It results from
excessive stimulation of glutamate receptors and involves both calcium influx and stressactivated
protein kinases (SAPKs), though the relationship between these events is poorly
defined. RhoGTPases are major regulators of SAPK activation but their contribution to
excitotoxic cell death has not been reported. Indirect evidence implicates Rac/cdc42
RhoGTPases in neuronal death subsequent to NGF withdrawal, whereas RhoA is involved in
inhibition of neurite regeneration and release of amyloidogenic A#42 peptide. We find that
stimulation of glutamate receptors leads to activation of RhoGTPases in primary cultured
neurons cultured neurons. This activation is calcium-dependent and contributes to the rapid
glutamate-induced activation of p38 and the ensuing neuronal death that we find is dependent
on this kinase. However, RhoGTPases alone are not sufficient to induced cell death, revealing
that requirements in addition to the GTPase-mediated p38 activation exist for excitotoxic cell
death to proceed. These observations reveal RhoGTPases as novel and essential components
of the excitotoxic cell death pathway.
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