Hypochlorous acid causes caspase activation and apoptosis or growth arrest in human endothelial cells

被引:87
作者
Vissers, MCM [1 ]
Pullar, JM [1 ]
Hampton, MB [1 ]
机构
[1] Christchurch Sch Med, Free Rad Res Res Grp, Dept Pathol, Christchurch, New Zealand
关键词
DNA degradation; necrosis; phosphatidylserine;
D O I
10.1042/0264-6021:3440443
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have investigated the effect of hypochlorous acid (HOCl) on cultured human umbilical-vein endothelial cells and shown that, whereas higher concentrations cause rapid necrosis, smaller amounts of this oxidant induce apoptosis or growth arrest. Exposure to 20-40 nmol of HOCl per 1.2 x 10(5) cells initiated apoptosis that was determined morphologically, by the identification of apoptotic nuclei with Hoechst 33342, and by detection of phosphatidylserine on the outer membrane. Degraded DNA was detected by how cytometry. HOCl induced caspase activity; specific inhibition of caspases was shown to prevent apoptosis. No caspase activation could be detected with 50 nmol of HOCl per 1.2 x 10(5) cells, a dose that caused more extensive necrosis. Lower doses of HOCl, which did not cause cell death, resulted in a transient growth arrest that was apparent with as little as 5 nmol of HOCl per 1.2 x 105 cells. These results show that HOCl can modify cellular responses that are dependent on signal transduction pathways in a manner similar to that of other oxidants.
引用
收藏
页码:443 / 449
页数:7
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