Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 9
c-Jun N-terminal protein kinase signalling mediates lovastatin-induced neuroblasts
apoptosis.
María I. Cerezo-Guisado1, Luis J. García-Marín2, Alberto Álvarez-Barrientos3, Eva
Pérez-Lorenzo1, Ricardo Argent1, María J. Bragado1 and María J. Lorenzo1.
1Departamento de Bioquímica y Biología Molecular y Genética, 3Departamento de
Fisiología, Facultad de Veterinaria, Universidad de Extremadura, Cáceres. 2Centro
Nacional de Investigaciones Cardiovasculares, Madrid. Spain. E-mail:
mjlorenzo@unex.es
We have previously shown that lovastatin, a competitive HMG-CoA reductase inhibitor,
induces apoptosis in spontaneously immortalized rat brain neuroblasts. Many studies have
implicated the c-Jun N-terminal protein kinase (JNK) pathway as a key regulator of apoptosis.
The aim of this study was to investigate the role for JNK in neuroblasts apoptosis induced by
lovastatin. Treatment of neuroblasts with lovastatin increased JNK activity in a concentration-
and time-dependent manner. The activation of JNK preceded the induction of apoptosis, and
JNK activity remained elevated for at least 24 hr. Lovastatin also increased c-Jun
phosphorylation and AP-1 DNA-binding activity in a concentration- and time-dependent
manner. Lovastatin effects were fully prevented by mevalonate, the final product of HMG-
CoA reductase. To examine whether the activation of JNK is involved in the process of
lovastatin-induced neuroblasts apoptosis, we utilized JNK inhibitor I, a specific inhibitor for
JNK. JNK inhibition prevented the morphological changes, the appearance of
internucleosomal DNA fragmentation, the increase in the percentage of apoptotic neuroblasts
and the amount of the activated form of caspase-3 elicited by lovastatin. In all the
experiments tested, JNK inhibitor effects were concentration-dependent. Taken together,
these data suggest that lovastatin may induce neuroblasts apoptosis by activating the JNKdependent
cell death pathway.
This work has been supported by Grants, SAF 2001-0154 (MCYT) and 2PR01B007 (JUEX).
M. I. Cerezo-Guisado is supported by a doctoral fellowship from Junta de Extremadura.
- 467 -