TY - JOUR
T1 - Decreased expression of bcl-2 and bcl-x mRNA coincides with apoptosis following intracerebral administration of 3-nitropropionic acid
AU - Sato, Shuzo
AU - Gobbel, Glenn T.
AU - Honkaniemi, Jari
AU - Li, Yibing
AU - Kondo, Takeo
AU - Murakami, Kensuke
AU - Sato, Minako
AU - Copin, Jean Christophe
AU - Sharp, Frank R.
AU - Chan, Pak H.
N1 - Funding Information:
The authors would like to thank S. Chen, B. Calagui, and L. Reola for their technical assistance. This study was supported by National Institutes of Health grants CA 13525, NS 35782, NS 14543, NS 25372, and NS 36147.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/10/12
Y1 - 1998/10/12
N2 - 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.
AB - 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.
KW - 3-Nitropropionic acid
KW - Apoptosis
KW - Huntington's disease
KW - Mitochondria
KW - bcl- 2
KW - bcl-x
KW - c-jun
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U2 - 10.1016/S0006-8993(98)00784-7
DO - 10.1016/S0006-8993(98)00784-7
M3 - Article
C2 - 9795133
AN - SCOPUS:0032511838
VL - 808
SP - 56
EP - 64
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -