Altered expression of bcl-2, bcl-X, bax, and c-fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats
Altered expression of bcl-2, bcl-X, bax, and c-fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats
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DOI：
10.1016/0169-328x(96)00059-9
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发表时间：
1996-09-01
期刊：
影响因子：
--
通讯作者：
Kuschinsky, W
中科院分区：
文献类型：
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作者：
Gillardon, F;Lenz, C;Kuschinsky, W
大鼠大脑中动脉的永久闭塞被用来评估局灶性缺血对bcl-2家族成员表达的影响，bcl-2家族成员参与了程序性细胞死亡的调节。一条大脑中动脉的管腔内闭塞6小时导致在同侧尾壳核、基底外侧皮质和部分丘脑内的组织学可检测的脑损伤。锌梗死的基底外侧皮质和丘脑的DNA片段检测到在许多核中使用原位末端标记的DNA断裂的末端转移酶，而只有分散的标记核可见于梗死的尾壳核。免疫组织化学分析显示，c-Fos的激活，在梗死的皮质和丘脑和非梗死扣带回皮质已被其他人所示。Bcl-2和Bcl-X的免疫反应性降低，Bax的免疫染色增加，观察到只在缺血皮质和丘脑内的神经元。然而，在梗死的尾壳核内，所有bcl-2家族成员的蛋白水平下降，c-Fos仍然不存在。逆转录和聚合酶链反应结果显示，在同侧大脑半球，bcl-2 mRNA水平明显降低，而bax mRNA水平升高。这些研究结果表明，细胞死亡抑制因子Bcl-2细胞死亡效应Bax的比例和伴随的激活c-Fos的转变可能有助于在梗死的丘脑和皮质神经元凋亡。
Permanent occlusion of the middle cerebral artery in rats was used to assess the effects of focal ischemia on the expression of members of the bcl-2 family which have been implicated in the regulation of programed cell death. intraluminal occlusion of one middle cerebral artery for 6 h resulted in histologically detectable brain damage within the ipsilateral caudate putamen, basolateral cortex and parts of the thalamus. Zn the infarcted basolateral cortex and thalamus fragmentation of DNA was detected in many nuclei using in-situ end-labeling of DNA breaks by terminal transferase, whereas only scattered labeled nuclei were visible in the infarcted caudate putamen. Immunohistochemical analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in the non-infarcted cingulate cortex as has been shown by others. A decrease in immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax was observed exclusively in neurons within the ischemic cortex and thalamus. Within the infarcted caudate putamen, however, protein levels of all bcl-2 family members declined and c-Fos remained absent. By reverse transcription and polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was elevated. These findings suggest that a shift in the ratio of cell death repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos may contribute to neuronal apoptosis in the infarcted thalamus and cortex.