Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1
Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1
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DOI：
10.1016/j.canlet.2006.09.009
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发表时间：
2007-05-08
期刊：
影响因子：
9.7
通讯作者：
Reiners, John J., Jr.
中科院分区：
文献类型：
--
作者：
Kessel, David;Reiners, John J., Jr.
暴露于LD 90浓度的Bcl-2/Bcl-x（L）拮抗剂HA 14 -1的L1210鼠白血病细胞迅速发生凋亡，但也产生许多具有双膜的细胞内空泡，表现出单丹酰尸胺的增强标记，并将胞质蛋白LC 3-I转化为LC 3-II。这些都是自噬的特征。自噬空泡在凋亡核形态出现之前迅速发展，并且可以在非凋亡和凋亡细胞中观察到。PI 3-激酶抑制剂渥曼青霉素抑制自噬促进细胞凋亡;相反，zDEVD-festrin抑制半胱天冬酶-3/7促进自噬。这两个过程都不依赖于钙的转运。这些结果表明，Bcl-2功能的药理学抑制可以模拟通过分子方法下调Bcl-2表达后可能发生的自噬诱导。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
L1210 murine leukemia cells exposed to an LD90 concentration of the Bcl-2/Bcl-x(L) antagonist HA14-1 rapidly undergo apoptosis but also develop numerous intracellular vacuoles with double membranes, exhibit enhanced labeling by monodansylcadaverine, and convert the cytosolic protein LC3-I to LC3-II. These are hallmarks of autophagy. Autophagic vacnotes develop rapidly, preceding the appearance of an apoptotic nuclear morphology and can be observed in both non-apoptotic and apoptotic cells. Inhibition of autophagy by the PI 3-kinase inhibitor wortmannin promoted apoptosis; conversely inhibition of caspase-3/7 with zDEVD-fmk promoted autophagy. Neither process was dependent on calcium translocation. These results indicate that pharmacological suppression of Bcl-2 function can mimic the induction of autophagy that can occur following the down-regulation of Bcl-2 expression by molecular approaches. (c) 2006 Elsevier Ireland Ltd. All rights reserved.