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Cleavage of focal adhesion proteins and PKCδ during lovastatin‐induced apoptosis in spontaneously immortalized rat brain neuroblasts
Author(s) -
GonzálezFernández Lauro,
CerezoGuisado Maria Isabel,
Langmesser Sonja,
Bragado Maria Julia,
Lorenzo Maria Jesús,
GarcíaMarín Luis Jesús
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.05023.x
Subject(s) - neuroblast , lovastatin , apoptosis , microbiology and biotechnology , cleavage (geology) , focal adhesion , protein kinase c , chemistry , biology , signal transduction , biochemistry , cholesterol , neurogenesis , paleontology , fracture (geology)
We have previously shown that lovastatin induces apoptosis in spontaneously immortalized rat brain neuroblasts. Focal adhesion proteins and protein kinase Cδ (PKCδ) have been implicated in the regulation of apoptosis. We found that lovastatin exposure induced focal adhesion kinase, Crk‐associated substrate (p130 Cas ), PKCδ cleavage and caspase‐3 activation in a concentration‐dependent manner. Lovastatin effects were fully prevented by mevalonate. The cleavage of p130 Cas was almost completely inhibited by z‐DEVD‐fmk, a specific caspase‐3 inhibitor, and z‐VAD‐fmk, a broad spectrum caspase inhibitor, indicating that cleavage is mediated by caspase‐3. In contrast, the lovastatin‐induced cleavage of PKCδ was only blocked by z‐VAD‐fmk suggesting that PKCδ cleavage is caspase‐dependent but caspase‐3‐independent. Additionally, z‐VAD‐fmk partially prevented lovastatin‐induced neuroblast apoptosis. The present data show that lovastatin may induce neuroblast apoptosis by both caspase‐dependent and independent pathways. These findings may suggest that the caspase‐dependent component leading to the neuroblast cell death is likely to involve the cleavage of focal adhesion proteins and PKCδ, which may be partially responsible for some biochemical features of neuroblast apoptosis induced by lovastatin.