Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death
Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death
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DOI：
10.1016/j.bbrc.2005.05.151
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发表时间：
2005-07-29
影响因子：
3.1
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Watanabe, T;Otsu, K;Hori, M
缺血再灌注心脏心肌细胞死亡的分子基础仍有待阐明。凋亡信号调节激酶I （Apoptosis signal- regulatory kinase I, ASK I）是一种丝裂原激活的蛋白激酶激酶激酶，在应激诱导的细胞凋亡中起重要作用。我们以ASKl（-/-）小鼠为研究对象，探讨ASKl在缺血再灌注损伤中的作用。在野生型心脏中，缺血再灌注导致坏死损伤，而在ASKl（-/-）心脏中，梗死面积急剧缩小。坏死损伤不伴有凋亡的迹象，如tunel阳性细胞增加、DNA断裂或caspase-3的激活。与野生型细胞相比，ASKl（-/-）心肌细胞对H2O2-或Ca2+诱导的凋亡和非凋亡细胞死亡更具抗性。这些数据表明ASKl参与坏死和凋亡，ASKl依赖性坏死可能导致缺血再灌注心脏的心肌细胞死亡。(c) 2005爱思唯尔公司版权所有。
The molecular basis of myocardial cell death in the ischernia-reperfused heart still remains to be clarified. Apoptosis signal-regulating kinase I (ASK I) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We studied ASKl(-/-) mice to examine the role of ASKl in ischemia-reperfusion injury. In the wild-type heart, ischemia-reperfusion resulted in necrotic injury, whereas infarct size was drastically reduced in the ASKl(-/-) heart. The necrotic injury was not accompanied with any evidence of apoptosis such as an increase in TUNEL-positive cells, DNA fragmentation or the activation of caspase-3. ASKl(-/-) cardiomyocytes were more resistant to H2O2- or Ca2+-induced apoptotic and non-apoptotic cell death compared with wild-type cells. These data suggest that ASKl is involved in necrosis as well as apoptosis and that ASKl-dependent necrosis is likely to contribute to myocardial cell death in the ischemia-reperfused heart. (c) 2005 Elsevier Inc. All rights reserved.