Serine protease inhibitor Spi2 mediated apoptosis of olfactory neurons
Abstract
The olfactory epithelium of adult mouse, where primary sensory neurons are massively committed to apoptosis by removal of their synaptic target, was used as a model to determine in vivo mechanisms for neuronal cell death induction. A macro-array assay revealed that the death of olfactory neurons is accompanied with over-expression of the serine protease inhibitor Spi2. This over-expression is associated with decreased serine protease activity in the olfactory mucosa. Moreover, in vitro or in vivo inhibition of serine proteases induced apoptotic death of olfactory neuronal cells. Interestingly, Spi2 over-expression is not occurring in olfactory neurons but in cells of the lamina propria, suggesting that Spi2 may act extracellularly as a cell death inducer. In that sense, we present evidence that in vitro Spi2 overexpression generates a secreted signal for olfactory neuron death. Hence, taken together these results document a possible novel mechanism for apoptosis induction that might occur in response to neurodegenerative insults.
Keywords
Serine protease inhibitor cell death olfactory neurons paracrine axotomy Abbreviations: NGF
nerve growth factor GDNF
glial derived neurotrophic factor TPCK
N-a-tosyl-L-phenylalanine chloromethyl ketone TLCK
N-a tosyl-L-lysine chloromethyl ketone) GFAP
glial ®brillary acidic protein DCC
deleted in colorectal cancer)
Serine protease inhibitor
cell death
olfactory neurons
paracrine
axotomy Abbreviations: NGF
nerve growth factor
GDNF
glial derived neurotrophic factor
TPCK
N-a-tosyl-L-phenylalanine chloromethyl ketone
TLCK
N-a tosyl-L-lysine chloromethyl ketone)
GFAP
glial ®brillary acidic protein
DCC
Domains
Life Sciences [q-bio]Origin | Files produced by the author(s) |
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