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.
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Abbreviations
- NGF:
-
nerve growth factor
- GDNF:
-
glial derived neurotrophic factor
- TPCK:
-
N-α-tosyl-L-phenylalanine chloromethyl ketone
- TLCK:
-
N-α tosyl-L-lysine chloromethyl ketone)
- GFAP:
-
glial fibrillary acidic protein
- DCC:
-
deleted in colorectal cancer)
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Acknowledgements
We thank Laure Granger, Nathalie Forey and Catherine Guix for excellent technical assistance. We wish to thank A LeCam for providing the Spi2 cDNA construct. L Pays was supported by a Ligue Nationale Contre le Cancer fellowship. This work was supported by the CNRS, the Ligue Nationale Contre le Cancer, the FRM, the ARC (9036,9340), the ‘emergence’ program.
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Thiemmara, V., Pays, L., Danty, E. et al. Serine protease inhibitor Spi2 mediated apoptosis of olfactory neurons. Cell Death Differ 9, 1343–1351 (2002). https://doi.org/10.1038/sj.cdd.4401098
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DOI: https://doi.org/10.1038/sj.cdd.4401098
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