Caspase-3-dependent and -independent apoptosis in focal brain ischemia
Caspase-3-dependent and -independent apoptosis in focal brain ischemia
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DOI：
10.1007/bf03402015
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发表时间：
2002-07-01
影响因子：
5.7
通讯作者：
Baskin, DS
中科院分区：
文献类型：
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作者：
Didenko, VV;Ngo, H;Baskin, DS
背景资料：尽管在新生大鼠的实验性脑缺血中已经证实了广泛的半胱天冬酶-3活化，但是由于半胱天冬酶-3在成年大鼠脑中的水平极低，因此该半胱天冬酶在成年脑的局灶性缺血中所起的作用尚不清楚。这就提出了一个问题，在永久性脑缺血（一种损害细胞蛋白质合成的情况）中，半胱天冬酶-3的合成和激活是否是执行凋亡程序和DNA片段化所必需的。采用大鼠大脑中动脉永久性闭塞模型，分别于6、24、48、49结果：永久性局灶性脑缺血的脑组织出现坏死和两种程序性细胞死亡（PCD）。第一种类型的PCD由活性半胱天冬酶-3和DFF 40/CAD阳性细胞代表。第二类PCD以caspase-3和DFF 40/CAD阴性细胞为代表，其显示出凋亡样PCD的形态学标志：即，核染色质凝聚在团块中和凋亡小体形成。第一种类型的细胞在缺血24小时后具有最大数量。第二类细胞主要见于缺血48和72小时后。坏死细胞，这也是检测到中风，caspase-3阴性，并有肿胀的细胞核，没有染色质凝聚和凋亡小体formation.Conclusions：我们的研究结果表明，在永久性脑缺血成年大鼠，PCD过程中发生不同的缺血区的各个部分。在严重能量消耗的条件下，细胞解体和包装成凋亡小体的反应在没有半胱天冬酶-3表达或半胱天冬酶-3依赖性脱氧核糖核酸酶活化的情况下完成。
Background: Although extensive caspase-3 activation has been demonstrated in experimental brain ischemia produced in neonatal rat, the role this caspase plays in the focal ischemia of adult brain is not clear, as the levels of caspase-3 in adult rat brain are extremely low. This raises the question whether caspase-3 synthesis and activation are essential for execution of the apoptotic program and DNA fragmentation in permanent brain ischemia, a condition that impairs cellular protein synthesis.Materials and Methods: Rat middle cerebral artery was permanently occluded and histochemical detection of procaspase-3, active caspase-3 and DFF40/CAD and apoptotic morphology analysis were performed at 6, 24, 48, and 72 hours after occlusion.Results: Necrosis and two types of programmed cell death (PCD) are identified in this study of permanent focal brain ischemia. The first type of PCD is represented by active caspase-3 and DFF40/CAD -positive cells. The second type of PCD is represented by caspase-3 and DFF40/CAD negative cells, which display morphological signs of apoptosis-like PCD: namely, nuclear chromatin condensation in lump masses and apoptotic body formation. The cells of the first type have a maximum number noted after 24 hours of ischemia. The cells of the second type are primarily seen after 48 and 72 hours of ischemia. Necrotic cells, which are also detected in the stroke, are caspase-3 negative, and have swollen nuclei, without chromatin condensation and apoptotic body formation.Conclusions: Our results indicate that in permanent brain ischemia in adult rats, PCD processes occur differently in various parts of ischemic zone. in conditions of severe energy depletion, the reactions of cellular disassembly and packaging into apoptotic bodies are accomplished without either caspase-3 expression or the activation of caspase-3-dependent deoxyribonuclease.