Differentially displayed genes in neuroblastoma cells treated with a mitochondrial toxin: evidence for possible involvement of ICAM-1 in 3-nitropropionic acid-mediated neurodegeneration

The mitochondrial toxin 3-nitropropionic acid (3-NPA) causes neurodegenerat ion in the basal ganglia and neurological symptoms resembling Huntington's disease (HD) when applied to primates or rodents, and therefore might be us ed as an animal model for this disorder. For that reason, the molecular mec hanisms involved in 3-NPA-induced neurodegeneration are of considerable int erest. In our model, murine neuroblastoma cells (Neuro-2a) were treated wit h different doses of 3-NPA, and changes in gene expression were analyzed by means of mRNA differential display (DDRT-PCR). Using 18 primer combination s, we have identified a set of 33 candidate cDNAs deriving from 29 excised DDRT bands whose expression appeared to be changed in response to the 3-NPA insult (mostly elevated). DNA sequencing revealed that novel, as well as p reviously described genes, are included in this panel. Amongst the known cD NAs, the differential mRNA expression of the ribosomal proteins S6 and L40, of the protein kinase A (PKA) catalytic beta subunit and of the intercellu lar adhesion molecule ICAM-I could be verified using Northern hybridization and RT-PCR, respectively. Furthermore, ICAM-I expression could also be sho wn to increase at the protein level, which points to a possible Function fo r this molecule in neuronal cells in the course of neurodegeneration. The r esults may prove useful in elucidating the multiple processes causing neuro degeneration subsequent to lesions by mitochondrial toxins and excitotoxins as well. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.