Sato S, Gobbel G T, Honkaniemi J, Li Y, Kondo T, Murakami K, Sato M, Copin J C, Sharp F R, Chan P H
Department of Neurological Surgery, University of California, San Francisco, CA 94143-0651, USA.
Brain Res. 1998 Oct 12;808(1):56-64. doi: 10.1016/s0006-8993(98)00784-7.
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.
线粒体毒素3-硝基丙酸（3-NP）是琥珀酸脱氢酶的不可逆抑制剂，可在体外和体内诱导细胞凋亡。我们将3-NP注入大鼠纹状体，以研究可抑制细胞凋亡的Bcl-2或Bcl-x蛋白在3-NP所致脑损伤中的潜在作用。纹状体组织的电泳检查表明，3-NP诱导了典型的凋亡核小体间断裂。基于末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）法染色，也有凋亡的组织学证据。注射后6小时首次观察到凋亡，1天时达到最大值，7天时仍可观察到。使用原位杂交在注射后1、3、6和12小时以及1、3、5和7天评估bcl-2、bcl-x和c-jun mRNA的表达。纹状体中bcl-2和bcl-x mRNA的表达从注射后6小时开始下降，并持续至5天。这与c-jun表达的明显增加形成对比。凋亡时间进程与bcl-2和bcl-x mRNA抑制时间进程的相似性表明，这些基因表达的变化可能导致3-NP注射后的细胞凋亡。
