文章基本信息

标题：DT40 cells lacking the Ca2+-binding protein annexin 5 are resistant to Ca2+-dependent apoptosis
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作者：Timothy E. Hawkins ; Debipriya Das ; Barry Young 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：12
页码：8054-8059
DOI：10.1073/pnas.132598099
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Annexins are widely expressed Ca2+-dependent phospholipid-binding proteins with poorly understood physiological roles. Proposed functions include Ca2+ channel activity and vesicle trafficking, but neither have been proven in vivo. Here we used targeted gene disruption to generate B-lymphocytes lacking annexin 5 (Anx5) expression and show that this results in reduced susceptibility to a range of apoptotic stimuli. By comparison B-lymphocytes lacking annexin 2 (Anx2) showed no such resistance, providing evidence that this effect is specific to loss of Anx5. The defect in the ANX5-/- cells occurs early in the apoptotic program before nuclear condensation, caspase 3 activation, and cell shrinkage, but downstream of an initial Ca2+ influx. Only UVA/B irradiation induced similar levels of apoptosis in wild-type and ANX5-/- cells. Unexpectedly, ANX5-/- cells permeabilized in vitro also failed to release mitochondrial cytochrome C, suggesting a possible mechanism for their resistance to apoptosis. These findings demonstrate a role for Anx5 in determining the susceptibility of B-lymphocytes to apoptosis.