Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?
Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?
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DOI：
10.1007/s10495-014-1004-1
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发表时间：
2014-05
期刊：
影响因子：
7.2
通讯作者：
K. Bannert;A. Kuhla;K. Abshagen;B. Vollmar
中科院分区：
文献类型：
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作者：
K. Bannert;A. Kuhla;K. Abshagen;B. Vollmar
各种数据表明细胞凋亡是肝损伤的一个关键特征，这促使研究人员在实验模型中研究抗凋亡策略的治疗潜力。然而，对凋亡细胞死亡在肝损伤中的作用的高估已经影响了实验模型中抗凋亡方案所提供的保护的临床转化。因此，细胞凋亡调节作为人类肝脏损伤的潜在治疗策略的希望无法得到证实。在此，我们评估了与人类病理生理学相关的不同肝应激模型中的细胞凋亡程度。使用细胞凋亡的形态学标准、Caspase-3 激活以及 TUNEL 测定与肝损伤中细胞凋亡的阳性对照相结合，我们量化了区分实质细胞和非实质细胞的凋亡细胞死亡，并通过裂解的 caspase-3 和 PARP-1 蛋白表达证实了这些结果。讨论我们的发现并将其与关于细胞凋亡的潜在作用的现有文献联系起来，我们强烈建议重新考虑抗凋亡策略以有效改善肝损伤。
A variety of data suggesting apoptotic cell death as a key feature of liver injury stimulated researchers to investigate the therapeutic potential of anti-apoptotic strategies in experimental models. However, the overestimated role of apoptotic cell death in liver injury has tempered the clinical translation of the protection afforded by anti-apoptotic regimes in experimental models. Thus, the hope for apoptosis modulation as potential treatment strategy for injured liver in humans could not be confirmed. Herein, we evaluated the degree of apoptosis in different hepatic stress models which are relevant for the human pathophysiology. Using morphological criteria of apoptosis, caspase-3 activation as well as TUNEL assay in combination with a positive control of apoptosis in liver injury, we quantified apoptotic cell death discriminating between parenchymal and non-parenchymal cells and confirmed these results by cleaved caspase-3 and PARP-1 protein expression. Discussing our findings and relating them to the existing literature on the potential role of apoptotic cell death, we strongly recommend reconsidering anti-apoptotic strategies to ameliorate liver injury efficiently.