Decreased expression of bcl - 2 and bcl - x mRNA coincides with apoptosis following intracerebral admin - istration of 3 - nitropropionic acid

The mitochondrial toxin, 3-nitropropionic acid (3-NP), is an irreversible inhibitor of succinate dehydrogenase that induces apoptosis in vitro and in vivo. We injected 3-NP into the striatum of rats to examine the potential role of Bcl-2 or Bcl-x, proteins that can inhibit apoptosis, in brain injury due to 3-NP. Electrophoretic examination of striatal tissue indicated that 3-NP induced internucleosomal fragmentation typical of apoptosis. There was also histologic evidence of apoptosis based on staining by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) method. Apoptosis was first observed 6 h after injection, was maximal at 1 day, and was still observed on day 7. Expression of bcl-2, bcl-x, and c-jun mRNA expression was evaluated 1, 3, 6, and 12 h and 1, 3, 5, and 7 days after injection using in situ hybridization. Both bcl-2 and bcl-x mRNA expression in the striatum decreased starting at 6 h and continued to 5 days after injection. This was in contrast to an apparent increase in c-jun expression. The similarity in the time course of apoptosis to that of suppression of bcl-2 and bcl-x mRNA suggests that changes in expression of these genes may contribute to apoptosis following 3-NP injection. (C) 1998 Published by Elsevier Science B.V. All rights reserved.