Decreased expression of bcl-2 and bcl-x mRNA coincides with apoptosis following intracerebral administration 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.
Sato
S
S
Department of Neurological Surgery, University of California, San Francisco, CA 94143-0651, USA.
Gobbel
G T
GT
Honkaniemi
J
J
Li
Y
Y
Kondo
T
T
Murakami
K
K
Sato
M
M
Copin
J C
JC
Sharp
F R
FR
Chan
P H
PH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007839:Functional Laterality; D019254:Genes, bcl-2; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D009574:Nitro Compounds; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D011422:Propionates; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D051020:bcl-X Protein; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid